{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T06:07:36Z","timestamp":1784354856923,"version":"3.55.0"},"reference-count":112,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,4]],"date-time":"2021-12-04T00:00:00Z","timestamp":1638576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Nestin is a member of the intermediate filament family, which is expressed in a variety of stem or progenitor cells as well as in several types of malignancies. Nestin might be involved in tissue homeostasis or repair, but its expression has also been associated with processes that lead to a poor prognosis in various types of cancer. In this article, we review the literature related to the effect of nestin expression in the lung. According to most of the reports in the literature, nestin expression in lung cancer leads to an aggressive phenotype and resistance to chemotherapy as well as radiation treatments due to the upregulation of phenomena such as cell proliferation, angiogenesis, and metastasis. Furthermore, nestin may be involved in the pathogenesis of some non-cancer-related lung diseases. On the other hand, evidence also indicates that nestin-positive cells may have a role in lung homeostasis and be capable of generating various types of lung tissues. More research is necessary to establish the true value of nestin expression as a prognostic factor and therapeutic target in lung cancer in addition to its usefulness in therapeutic approaches for pulmonary diseases.<\/jats:p>","DOI":"10.3390\/cells10123413","type":"journal-article","created":{"date-parts":[[2021,12,5]],"date-time":"2021-12-05T20:59:33Z","timestamp":1638737973000},"page":"3413","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Nestin-Expressing Cells in the Lung: The Bad and the Good Parts"],"prefix":"10.3390","volume":"10","author":[{"given":"Gilberto","family":"Jaramillo-Rangel","sequence":"first","affiliation":[{"name":"Department of Pathology, School of Medicine, Autonomous University of Nuevo Le\u00f3n, Monterrey 64460, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda-de-Lourdes","family":"Ch\u00e1vez-Briones","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Autonomous University of Nuevo Le\u00f3n, Monterrey 64460, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Ancer-Arellano","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Autonomous University of Nuevo Le\u00f3n, Monterrey 64460, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Ortega-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Autonomous University of Nuevo Le\u00f3n, Monterrey 64460, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sharma, P., Alsharif, S., Fallatah, A., and Chung, B.M. (2019). Intermediate Filaments as Effectors of Cancer Development and Metastasis: A Focus on Keratins, Vimentin, and Nestin. Cells, 8.","DOI":"10.3390\/cells8050497"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1002\/cm.21597","article-title":"Intermediate filaments in developing neurons: Beyond structure","volume":"77","author":"Bott","year":"2020","journal-title":"Cytoskeleton"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1007\/s00018-018-2794-z","article-title":"Nestin-expressing progenitor cells: Function, identity and therapeutic implications","volume":"75","author":"Bernal","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1101\/gad.1552107","article-title":"Intermediate filament scaffolds fulfill mechanical, organizational, and signaling functions in the cytoplasm","volume":"21","author":"Kim","year":"2007","journal-title":"Genes Dev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev-cellbio-100617-062534","article-title":"Cytoplasmic Intermediate Filaments in Cell Biology","volume":"34","year":"2018","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"47807","DOI":"10.1074\/jbc.M107692200","article-title":"Nestin Is a Neuroepithelial Target Gene of Thyroid Transcription Factor-1, a Homeoprotein Required for Forebrain Organogenesis","volume":"276","author":"Lonigro","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1111\/j.1432-0436.2005.00050.x","article-title":"Human fibroblast-derived cell lines have characteristics of embryonic stem cells and cells of neuro-ectodermal origin","volume":"73","author":"Rieske","year":"2005","journal-title":"Differentiation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.devbrainres.2005.01.012","article-title":"Partial rescue of neonatal lethality of Dhcr7 null mice by a nestin promoter-driven DHCR7 transgene expression","volume":"156","author":"Yu","year":"2005","journal-title":"Brain Res. Dev. Brain Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1002\/dvg.20226","article-title":"Nestin-Cre transgenic mouse line Nes-Cre1 mediates highly efficient Cre\/loxP mediated recombination in the nervous system, kidney, and somite-derived tissues","volume":"44","author":"Dubois","year":"2006","journal-title":"Genesis"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1089\/scd.2004.13.658","article-title":"Nestin expression by newly formed human blood vessels","volume":"13","author":"Filip","year":"2004","journal-title":"Stem Cells Dev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.tice.2009.05.004","article-title":"Characterization of mesenchymal stem cells (MSCs) from human fetal lung: Potential differentiation of germ cells","volume":"41","author":"Hua","year":"2009","journal-title":"Tissue Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3331","DOI":"10.3892\/mmr.2015.3854","article-title":"Isolation, in vitro culture and identification of a new type of mes-enchymal stem cell derived from fetal bovine lung tissues","volume":"12","author":"Hu","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1002\/jcb.26368","article-title":"Expression of nestin in embryonic tissues and its effects on clinicopathological characteristics of patients with placenta previa","volume":"119","author":"Qiao","year":"2018","journal-title":"J. Cell. Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"L102","DOI":"10.1152\/ajplung.00511.2017","article-title":"Neuropilin-1 and platelet-derived growth factor receptors cooperatively regulate intermediate filaments and mesenchymal cell migration during alveolar septation","volume":"315","author":"McGowan","year":"2018","journal-title":"Am. J. Physiol. Cell. Mol. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1038\/labinvest.3700300","article-title":"Human bronchial fibroblasts exhibit a mesenchymal stem cell phenotype and multilineage differentiating potentialities","volume":"85","author":"Sabatini","year":"2005","journal-title":"Lab. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ricciardi, M., Malpeli, G., Bifari, F., Bassi, G., Pacelli, L., Kamdje, A.H.N., Chilosi, M., and Krampera, M. (2012). Comparison of Epithelial Differentiation and Immune Regulatory Properties of Mesenchymal Stromal Cells Derived from Human Lung and Bone Marrow. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035639"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/aps.2013.50","article-title":"Mesenchymal stem cells: A new trend for cell therapy","volume":"34","author":"Wei","year":"2013","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3389\/fbioe.2020.00043","article-title":"Therapeutic Potential of Mesenchymal Stem Cells for Cancer Therapy","volume":"8","author":"Hmadcha","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1002\/cbin.10031","article-title":"Evidence of chondrocyte turnover in lung cartilage, with the probable participation of nestin-positive cells","volume":"37","year":"2013","journal-title":"Cell Biol. Int."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"151","DOI":"10.4067\/S0717-95022014000100026","article-title":"Nestin-positive Stem Cells Participate in Chondrocyte Renewal in Healthy Adult Lung Cartilage","volume":"32","year":"2014","journal-title":"Int. J. Morphol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4197","DOI":"10.1007\/s00018-010-0498-0","article-title":"Cartilage biology, pathology, and repair","volume":"67","author":"Umlauf","year":"2010","journal-title":"Cell Mol. Life Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2679","DOI":"10.1111\/jcmm.12653","article-title":"Detection of a novel stem cell probably involved in normal turnover of the lung airway epithelium","volume":"19","year":"2015","journal-title":"J. Cell. Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s10735-007-9078-5","article-title":"The diffuse stellate cell system","volume":"38","author":"Zhao","year":"2007","journal-title":"J. Mol. Histol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"53302","DOI":"10.18632\/oncotarget.18396","article-title":"A combination of valproic acid sodium salt, CHIR99021, E-616452, tranylcypromine, and 3-Deazaneplanocin A causes stem cell-like characteristics in cancer cells","volume":"8","author":"Sha","year":"2017","journal-title":"Oncotarget"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/scrt512","article-title":"Type-1 pericytes accumulate after tissue injury and produce collagen in an organ-dependent manner","volume":"5","author":"Birbrair","year":"2014","journal-title":"Stem Cell Res. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1111\/j.1440-1827.2010.02532.x","article-title":"Heterogeneous expression of nestin in myofibroblasts of various human tissues","volume":"60","author":"Kishaba","year":"2010","journal-title":"Pathol. Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.pcad.2016.05.002","article-title":"Lung Capillary Stress Failure and Arteriolar Remodelling in Pulmonary Hypertension Associated with Left Heart Disease (Group 2 PH)","volume":"59","author":"Dayeh","year":"2016","journal-title":"Prog. Cardiovasc. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1801913","DOI":"10.1183\/13993003.01913-2018","article-title":"Hae-modynamic definitions and updated clinical classification of pulmonary hypertension","volume":"53","author":"Simonneau","year":"2019","journal-title":"Eur. Respir. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1002\/jcp.25257","article-title":"Endothelial and Epithelial Cell Transition to a Mesenchymal Phenotype Was Delineated by Nestin Expression","volume":"231","author":"Chabot","year":"2015","journal-title":"J. Cell. Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1183\/13993003.00574-2015","article-title":"Nestin-expressing vascular wall cells drive development of pulmonary hypertension","volume":"47","author":"Saboor","year":"2016","journal-title":"Eur. Respir. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1080\/01902148.2019.1605426","article-title":"Opposite alterations of endothelin-1 in lung and pulmonary artery mirror gene expression of bone morphogenetic protein receptor 2 in experimental pulmonary hypertension","volume":"45","author":"Veteskova","year":"2019","journal-title":"Exp. Lung Res."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Bhagwani, A.R., Hultman, S., Farkas, D., Moncayo, R., Dandamudi, K., Zadu, A.K., Cool, C.D., and Farkas, L. (2019). Endothelial cells are a source of Nestin expression in Pulmonary Arterial Hypertension. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0213890"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.yjmcc.2020.09.005","article-title":"Nestin represents a potential marker of pulmonary vascular remodeling in pulmonary arterial hypertension associated with congenital heart disease","volume":"149","author":"Zhou","year":"2020","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1002\/jcp.24696","article-title":"Nestin is a Marker of Lung Remodeling Secondary to Myocardial Infarction and Type I Diabetes in the Rat","volume":"230","author":"Chabot","year":"2015","journal-title":"J. Cell. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Hertig, V., Tardif, K., Meus, M.A., Duquette, N., Villeneuve, L., Toussaint, F., Ledoux, J., and Calderone, A. (2017). Nestin expression is upregulated in the fibrotic rat heart and is localized in collagen-expressing mesenchymal cells and interstitial CD31(+)- cells. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0176147"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Thies, S., Friess, M., Frischknecht, L., Korol, D., Felley-Bosco, E., Stahel, R., Vrugt, B., Weder, W., Opitz, I., and Soltermann, A. (2015). Expression of the Stem Cell Factor Nestin in Malignant Pleural Mesothelioma Is Associated with Poor Prognosis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0139312"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1016\/j.jaci.2018.08.023","article-title":"Ras homolog family member A\/Rho-associated protein kinase 1 signaling modulates lineage commitment of mesenchymal stem cells in asthmatic patients through lymphoid en-hancer-binding factor 1","volume":"143","author":"Ke","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.toxlet.2019.01.005","article-title":"Inhibition of mesenchymal stromal cells\u2019 chemotactic effect to ame-liorate paraquat-induced pulmonary fibrosis","volume":"307","author":"Zhang","year":"2019","journal-title":"Toxicol. Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLO-BOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.humpath.2009.10.018","article-title":"Expression of nestin in lymph node metastasis and lymphangiogenesis in non-small cell lung cancer patients","volume":"41","author":"Chen","year":"2010","journal-title":"Hum. Pathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"321","DOI":"10.5507\/bp.2010.048","article-title":"Identification of CD133+\/nestin+ putative cancer stem cells in non-small cell lung cancer","volume":"154","author":"Janikova","year":"2010","journal-title":"Biomed. Pap. Med. Fac. Univ. Palacky Olomouc. Czech Repub."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1378\/chest.10-1121","article-title":"Prognostic Significance of Nestin Expression in Resected Non-small Cell Lung Cancer","volume":"139","author":"Ryuge","year":"2011","journal-title":"Chest"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"135","DOI":"10.5507\/bp.2012.036","article-title":"Analysis of the prognostic impact of nestin expression in non-small cell lung cancer","volume":"156","author":"Skarda","year":"2012","journal-title":"Biomed. Pap. Med. Fac. Univ. Palacky Olomouc. Czech Repub."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Chen, Z., Wang, J., Cai, L., Zhong, B., Luo, H., Hao, Y., Yu, W., Wang, B., Su, C., and Lei, Y. (2014). Role of the Stem Cell-Associated Intermediate Filament Nestin in Malignant Proliferation of Non-Small Cell Lung Cancer. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0085584"},{"key":"ref_45","first-page":"1392","article-title":"Nestin servers as a promising prognostic biomarker in non-small cell lung cancer","volume":"9","author":"Liu","year":"2017","journal-title":"Am. J. Transl. Res."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Ryuge, S., Sato, Y., Nagashio, R., Hiyoshi, Y., Katono, K., Igawa, S., Nakashima, H., Shiomi, K., Ichinoe, M., and Murakumo, Y. (2017). Prognostic significance of nestin expression in patients with resected non-small cell lung cancer treated with platinum-based adjuvant chemotherapy; relationship between nestin expression and epithelial to mes-enchymal transition related markers. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0173886"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.3892\/ijo.2014.2278","article-title":"Nestin regulates proliferation, migration, invasion and stemness of lung adenocarcinoma","volume":"44","author":"Narita","year":"2014","journal-title":"Int. J. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"29","DOI":"10.3109\/1354750X.2013.863975","article-title":"Evaluation of nestin in lung adenocarcinoma: Relation to VEGF and Bcl-2","volume":"19","author":"Ahmed","year":"2014","journal-title":"Biomarkers"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1097\/JTO.0000000000000021","article-title":"Putative Stem Cell Markers in Non\u2013Small-Cell Lung Cancer: A Clinicopathologic Characterization","volume":"9","author":"Sterlacci","year":"2014","journal-title":"J. Thorac. Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.lungcan.2013.04.022","article-title":"Involvement of intermediate filament nestin in cell growth of small-cell lung cancer","volume":"81","author":"Takakuwa","year":"2013","journal-title":"Lung Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.3389\/fonc.2020.01367","article-title":"Nestin Expression Affects Resistance to Chemotherapy and Clinical Outcome in Small Cell Lung Cancer","volume":"10","author":"Sone","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.lungcan.2012.03.025","article-title":"Prognostic impact of nestin expression in resected large cell neuroendocrine carcinoma of the lung","volume":"77","author":"Ryuge","year":"2012","journal-title":"Lung Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"291","DOI":"10.5114\/pjp.2017.73924","article-title":"Clinical significance of nestin and its as-sociation with survival in neuroendocrine lung tumours","volume":"68","author":"Brominska","year":"2017","journal-title":"Pol. J. Pathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1097\/MNM.0000000000000972","article-title":"18F-FDG PET\/CT and nestin expression as prognostic tools in pulmonary neu-roendocrine tumours","volume":"40","author":"Gabryel","year":"2019","journal-title":"Nucl. Med. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e18174","DOI":"10.1097\/MD.0000000000018174","article-title":"A typical carcinoid of the lung\u2014A case report with pathological correlation and propagation of the cancer stem cell line BKZ1 with synaptophysin expression","volume":"98","author":"Greiner","year":"2019","journal-title":"Medicine"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"22970","DOI":"10.18632\/oncotarget.4042","article-title":"Association of the intermediate filament nestin with cancer stage: A meta-analysis based on 223 positive\/high nestin cases and 460 negative\/low case-free controls","volume":"6","author":"Zhong","year":"2015","journal-title":"Oncotarget"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"34520","DOI":"10.18632\/oncotarget.9145","article-title":"Association of SOX2 and Nestin DNA amplification and protein expression with clinical features and overall survival in non-small cell lung cancer: A systematic review and me-ta-analysis","volume":"7","author":"Li","year":"2016","journal-title":"Oncotarget"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"800","DOI":"10.4103\/0973-1482.204901","article-title":"Nestin is significantly associated with the overall survival of nonsmall cell lung cancer: A meta-analysis","volume":"16","author":"Zhang","year":"2020","journal-title":"J. Cancer Res. Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s10238-016-0421-6","article-title":"Clinicopathological and prognostic significance of Nestin expression in patients with non-small cell lung cancer: A systematic review and meta-analysis","volume":"17","author":"Li","year":"2017","journal-title":"Clin. Exp. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"9199","DOI":"10.1158\/0008-5472.CAN-07-0806","article-title":"Roles for the stem cell asso-ciated intermediate filament nestin in prostate cancer migration and metastasis","volume":"67","author":"Kleeberger","year":"2007","journal-title":"Cancer Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"850","DOI":"10.3892\/ol.2015.3366","article-title":"Nestin expression as an independent indicator of poor prognosis for patients with anaplastic thyroid cancer","volume":"10","author":"Kurata","year":"2015","journal-title":"Oncol. Lett."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"40","DOI":"10.3892\/or.2014.3588","article-title":"Nestin predicts a favorable prognosis in early ampullary adenocarcinoma and functions as a promoter of metastasis in advanced cancer","volume":"33","author":"Shan","year":"2015","journal-title":"Oncol. Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.4161\/cc.9.6.11108","article-title":"Tumor initiating cells: Development and critical characterization of a model derived from the A431 carcinoma cell line forming spheres in suspension","volume":"9","author":"Bortolomai","year":"2010","journal-title":"Cell Cycle"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1111\/j.1349-7006.2009.01414.x","article-title":"Biological heterogeneity of putative bladder cancer stem-like cell populations from human bladder transitional cell carcinoma samples","volume":"101","author":"Bentivegna","year":"2010","journal-title":"Cancer Sci."},{"key":"ref_65","first-page":"485","article-title":"Expression of neural stem cell markers in malignant rhabdoid tumor cell lines","volume":"23","author":"Okuno","year":"2009","journal-title":"Oncol. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.drup.2016.06.006","article-title":"The bad seed: Cancer stem cells in tumor development and resistance","volume":"28","author":"Koren","year":"2016","journal-title":"Drug Resist. Updat."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"8381","DOI":"10.1002\/jcp.27740","article-title":"Cancer stem cells (CSCs) in cancer progression and therapy","volume":"234","author":"Najafi","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/s41392-020-00430-1","article-title":"Targeting cancer stem cells for reversing therapy resistance: Mechanism, signaling, and prospective agents","volume":"6","author":"Zhou","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"pe53","DOI":"10.1126\/stke.3662006pe53","article-title":"Intermediate Filaments as Signaling Platforms","volume":"2006","author":"Pallari","year":"2006","journal-title":"Sci. STKE"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1093\/jb\/mvp070","article-title":"Nestin serves as a prosurvival deter-minant that is linked to the cytoprotective effect of epidermal growth factor in rat vascular smooth muscle cells","volume":"146","author":"Huang","year":"2009","journal-title":"J. Biochem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.4161\/cc.7.10.5954","article-title":"Cancer stem cells and survival pathways","volume":"7","author":"Hambardzumyan","year":"2008","journal-title":"Cell Cycle"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1186\/s13058-014-0408-8","article-title":"Nestin positively regulates the Wnt\/\u03b2-catenin pathway and the proliferation, survival and invasiveness of breast cancer stem cells","volume":"16","author":"Zhao","year":"2014","journal-title":"Breast Cancer Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/1475-2867-14-57","article-title":"Contribution of nestin positive esophageal squamous cancer cells on malignant proliferation, apoptosis, and poor prognosis","volume":"14","author":"Zhong","year":"2014","journal-title":"Cancer Cell Int."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1159\/000367802","article-title":"Epithelial-Mesenchymal Transition and Drug Resistance: Role, Molecular Mechanisms, and Therapeutic Strategies","volume":"37","author":"Sui","year":"2014","journal-title":"Oncol. Res. Treat."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"110909","DOI":"10.1016\/j.biopha.2020.110909","article-title":"EMT, cancer stem cells and autophagy; The three main axes of metastasis","volume":"133","author":"Babaei","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1111\/j.1349-7006.2009.01419.x","article-title":"Epithelial-mesenchymal transition in cancer development and its clinical significance","volume":"101","author":"Iwatsuki","year":"2010","journal-title":"Cancer Sci."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Roche, J. (2018). The epithelial-to-mesenchymal transition in cancer. Cancers, 10.","DOI":"10.3390\/cancers10020052"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s13046-016-0387-y","article-title":"Nestin overexpression in hepatocellular carcinoma associates with epithelial-mesenchymal transition and chemoresistance","volume":"35","author":"Zhang","year":"2016","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11538-021-00859-7","article-title":"Modelling Cell Invasion: A Review of What JD Murray and the Embryo Can Teach Us","volume":"83","author":"Kulesa","year":"2021","journal-title":"Bull. Math. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"103245","DOI":"10.1016\/j.critrevonc.2021.103245","article-title":"The effects of vascularization on tumor development: A systematic review and me-ta-analysis of pre-clinical studies","volume":"159","author":"Esteves","year":"2021","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"409","DOI":"10.3748\/wjg.v17.i4.409","article-title":"Nestin in gastrointestinal and other cancers: Effects on cells and tumor angiogenesis","volume":"17","author":"Ishiwata","year":"2011","journal-title":"World J. Gastroenterol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"4005","DOI":"10.1158\/0008-5472.CAN-04-2970","article-title":"Metastasizing melanoma formation caused by expression of activated N-RasQ61K on an INK4a-deficient background","volume":"65","author":"Ackermann","year":"2005","journal-title":"Cancer Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1159\/000143401","article-title":"Expression of CD44 is associated with a metastatic pattern of human neuro-blastoma cells in a SCID mouse xenograft model","volume":"29","author":"Valentiner","year":"2008","journal-title":"Tumour Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1158\/1535-7163.MCT-14-0659","article-title":"Changes in BAI1 and Nestin Expression Are Prognostic Indicators for Survival and Metastases in Breast Cancer and Provide Opportunities for Dual Targeted Therapies","volume":"14","author":"Meisen","year":"2015","journal-title":"Mol. Cancer Ther."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"R87","DOI":"10.1186\/bcr2944","article-title":"Breast cancer biological subtypes and protein expression predict for the preferential distant me-tastasis sites: A nationwide cohort study","volume":"13","author":"Sihto","year":"2011","journal-title":"Breast Cancer Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.ajpath.2013.11.014","article-title":"Nestin delineates pancreatic cancer stem cells in met-astatic foci of NOD\/Shi-scid IL2R\u03b3(null) (NOG) mice","volume":"184","author":"Matsuda","year":"2014","journal-title":"Am. J. Pathol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1369\/jhc.2010.955609","article-title":"The Neural Stem\/Progenitor Cell Marker Nestin Is Expressed in Proliferative Endothelial Cells, but Not in Mature Vasculature","volume":"58","author":"Suzuki","year":"2010","journal-title":"J. Histochem. Cytochem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"C349","DOI":"10.1152\/ajpcell.00121.2014","article-title":"Nestin-mediated cytoskeletal remodeling in endothelial cells: Novel mechanistic insight into VEGF-induced cell migration in angiogenesis","volume":"308","author":"Liang","year":"2015","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"42","DOI":"10.3748\/wjg.v19.i1.42","article-title":"Nestin: A novel angiogenesis marker and possible target for tumor angiogenesis","volume":"19","author":"Matsuda","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"ref_90","first-page":"699","article-title":"Current insights into the association of Nestin with tumor angiogenesis","volume":"20","author":"Onisim","year":"2015","journal-title":"J. BUON"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"284","DOI":"10.4149\/neo_2009_04_284","article-title":"Analysis of VEGF, Flt-1, Flk-1, nestin and MMP-9 in relation to astrocytoma pathogenesis and progression","volume":"56","author":"Hlobilkova","year":"2009","journal-title":"Neoplasma"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1111\/nan.12097","article-title":"Study of stem cell marker nestin and its correlation with vascular endothelial growth factor and microvascular density in ependymomas","volume":"40","author":"Nambirajan","year":"2014","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_93","first-page":"45","article-title":"Correlation between glioblastoma stem-like cells and tumor vascularization","volume":"27","author":"Niu","year":"2021","journal-title":"Oncol. Rep."},{"key":"ref_94","first-page":"17","article-title":"The stem cell marker nestin predicts poor prognosis in human melanoma","volume":"23","author":"Piras","year":"2010","journal-title":"Oncol. Rep."},{"key":"ref_95","first-page":"1345","article-title":"Nestin as a novel therapeutic target for pancreatic cancer via tumor angiogenesis","volume":"40","author":"Ishiwata","year":"2012","journal-title":"Int. J. Oncol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1097\/00129039-200206000-00005","article-title":"Comparative Evaluation of Angiogenesis in Gastric Adenocarcinoma by Nestin and CD34","volume":"10","author":"Kim","year":"2002","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"ref_97","first-page":"593","article-title":"Identification of neovasculature using nestin in colorectal cancer","volume":"30","author":"Teranishi","year":"2007","journal-title":"Int. J. Oncol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1136\/gut.2008.176271","article-title":"High expression levels of putative hepatic stem\/progenitor cell biomarkers related to tumour angiogenesis and poor prognosis of hepatocellular carcinoma","volume":"59","author":"Yang","year":"2010","journal-title":"Gut"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"668","DOI":"10.3892\/ijo.2017.4057","article-title":"Nestin-positive microvessel density is an independent prognostic factor in breast cancer","volume":"51","author":"Nowak","year":"2017","journal-title":"Int. J. Oncol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"310","DOI":"10.4149\/neo_2012_040","article-title":"Expression of putative stem marker nestin and CD133 in advanced serous ovarian cancer","volume":"59","author":"Qin","year":"2012","journal-title":"Neoplasma"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"4708","DOI":"10.1158\/0008-5472.CAN-08-4417","article-title":"Proliferation of Immature Tumor Vessels Is a Novel Marker of Clinical Progression in Prostate Cancer","volume":"69","author":"Gravdal","year":"2009","journal-title":"Cancer Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1002\/cjp2.78","article-title":"Microvascular proliferation is associated with aggressive tumour features and reduced survival in lung adenocarcinoma","volume":"3","author":"Ramnefjell","year":"2017","journal-title":"J. Pathol. Clin. Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1038\/labinvest.3700186","article-title":"Angiogenic endothelium-specific nestin expression is enhanced by the first intron of the nestin gene","volume":"84","author":"Aihara","year":"2004","journal-title":"Lab. Investig."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1158\/1940-6207.CAPR-08-0095","article-title":"Growth inhibition and regression of lung tumors by silibinin: Modulation of angiogenesis by macrophage-associated cyto-kines and nuclear factor-kappaB and signal transducers and activators of transcription 3","volume":"2","author":"Tyagi","year":"2009","journal-title":"Cancer Prev. Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1158\/1078-0432.CCR-10-2290","article-title":"Silibinin prevents lung tumorigenesis in wild-type but not in iNOS-\/- mice: Potential of real-time micro-CT in lung cancer chemoprevention studies","volume":"17","author":"Ramasamy","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_106","first-page":"97","article-title":"Primer dosing of S. typhimurium A1-R potentiates tumor-targeting and efficacy in immunocompetent mice","volume":"33","author":"Tome","year":"2013","journal-title":"Anticancer. Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"5352","DOI":"10.1158\/0008-5472.CAN-05-0821","article-title":"Nestin-Linked Green Fluorescent Protein Transgenic Nude Mouse for Imaging Human Tumor Angiogenesis","volume":"65","author":"Amoh","year":"2005","journal-title":"Cancer Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s10585-006-9018-x","article-title":"Visualization of nascent tumor angiogenesis in lung and liver metastasis by differential dual-color fluorescence imaging in nestin-linked-GFP mice","volume":"23","author":"Amoh","year":"2006","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/j.trecan.2016.09.001","article-title":"The Emerging Role of Cdk5 in Cancer","volume":"2","author":"Pozo","year":"2016","journal-title":"Trends Cancer"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1111\/cas.12691","article-title":"Nestin as a marker of cancer stem cells","volume":"106","author":"Neradil","year":"2015","journal-title":"Cancer Sci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1593\/neo.06526","article-title":"Notch Signaling Enhances Nestin Expression in Gliomas","volume":"8","author":"Shih","year":"2006","journal-title":"Neoplasia"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.cell.2014.05.051","article-title":"p53-Dependent Nestin Regulation Links Tumor Suppression to Cellular Plasticity in Liver Cancer","volume":"158","author":"Tschaharganeh","year":"2014","journal-title":"Cell"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/12\/3413\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:39:38Z","timestamp":1760168378000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/12\/3413"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,4]]},"references-count":112,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["cells10123413"],"URL":"https:\/\/doi.org\/10.3390\/cells10123413","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,4]]}}}