{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T07:46:15Z","timestamp":1785915975193,"version":"3.56.0"},"reference-count":44,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T00:00:00Z","timestamp":1626998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["26893052"],"award-info":[{"award-number":["26893052"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["16K19709"],"award-info":[{"award-number":["16K19709"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>CD147, a transmembrane glycoprotein that belongs to the immunoglobulin superfamily, and cyclophilin A (CypA), one of the binding partners of CD147, are overexpressed in tumor cells and associated with the progression of several malignancies, including both solid and hematological malignancies. However, CD147 and CypA involvement in cutaneous T-cell lymphoma (CTCL) has not been reported. In this study, we examined CD147 and CypA expression and function using clinical samples of mycosis fungoides (MF) and S\u00e9zary syndrome (SS) and CTCL cell lines. CD147 and CypA were overexpressed by tumor cells of MF\/SS, and CypA was also expressed by epidermal keratinocytes in MF\/SS lesional skin. Serum CypA levels were increased and correlated with disease severity markers in MF\/SS patients. Anti-CD147 antibody and\/or anti-CypA antibody suppressed the proliferation of CTCL cell lines, both in vitro and in vivo, via downregulation of phosphorylated extracellular-regulated kinase 1\/2 and Akt. These results suggest that CD147-CypA interactions can contribute to the proliferation of MF\/SS tumor cells in both a autocrine and paracrine manner, and that the disruption of CD147-CypA interactions could be a new therapeutic strategy for the treatment of MF\/SS.<\/jats:p>","DOI":"10.3390\/ijms22157889","type":"journal-article","created":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T10:31:44Z","timestamp":1627036304000},"page":"7889","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["CD147-Cyclophilin a Interactions Promote Proliferation and Survival of Cutaneous T-Cell Lymphoma"],"prefix":"10.3390","volume":"22","author":[{"given":"Minami","family":"Sakamoto","sequence":"first","affiliation":[{"name":"Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1879-3128","authenticated-orcid":false,"given":"Tomomitsu","family":"Miyagaki","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan"},{"name":"Department of Dermatology, St. Marianna University School of Medicine, Kanagawa 216-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Kamijo","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7362-3207","authenticated-orcid":false,"given":"Tomonori","family":"Oka","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hikari","family":"Boki","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Takahashi-Shishido","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan"},{"name":"Department of Dermatology, International University of Health and Welfare, Chiba 286-8520, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiraku","family":"Suga","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Sugaya","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan"},{"name":"Department of Dermatology, International University of Health and Welfare, Chiba 286-8520, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichi","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3768","DOI":"10.1182\/blood-2004-09-3502","article-title":"WHO-EORTC classification for cutaneous lymphomas","volume":"105","author":"Willemze","year":"2005","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e49","DOI":"10.1111\/1346-8138.15707","article-title":"Outlines of the Japanese guidelines for the management of primary cutaneous lymphomas 2020","volume":"48","author":"Ohtsuka","year":"2021","journal-title":"J. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Nicolay, J.P., Albrecht, J.D., Alberti-Violetti, S., and Berti, E. (2021). CCR4 in cutaneous T-cell lymphoma: Therapeutic targeting of a pathogenic driver. Eur. J. Immunol., Online ahead of print.","DOI":"10.1002\/eji.202049043"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3766","DOI":"10.1200\/JCO.2015.61.7142","article-title":"Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and S\u00e9zary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model","volume":"33","author":"Scarisbrick","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"116","DOI":"10.3389\/fmed.2019.00116","article-title":"Novel and Future Therapeutic Drugs for Advanced Mycosis Fungoides and S\u00e9zary Syndrome","volume":"6","author":"Oka","year":"2019","journal-title":"Front. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s11864-020-00809-w","article-title":"Mycosis Fungoides and S\u00e9zary Syndrome: Updates and Review of Current Therapy","volume":"22","author":"Kamijo","year":"2021","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2798","DOI":"10.1182\/blood-2014-07-590398","article-title":"Interleukin-13 is overexpressed in cutaneous T-cell lymphoma cells and regulates their proliferation","volume":"125","author":"Geskin","year":"2015","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1182\/blood-2018-04-845834","article-title":"Aberrant CD137 ligand expression induced by GATA6 overexpression promotes tumor progression in cutaneous T-cell lymphoma","volume":"132","author":"Kamijo","year":"2018","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.jid.2019.09.007","article-title":"YKL-40 Promotes Proliferation of Cutaneous T-Cell Lymphoma Tumor Cells through Extracellular Signal-Regulated Kinase Pathways","volume":"140","author":"Suzuki","year":"2020","journal-title":"J. Investig. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/s41375-019-0622-6","article-title":"Thrombospondin-1 promotes tumor progression in cutaneous T-cell lymphoma via CD47","volume":"34","author":"Kamijo","year":"2020","journal-title":"Leukemia"},{"key":"ref_11","first-page":"adv00059","article-title":"Increased Expression of Delta-like Ligand 4 in Mycosis Fungoides","volume":"100","author":"Boki","year":"2020","journal-title":"Acta Derm. Venereol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1093\/oxfordjournals.jbchem.a123045","article-title":"Basigin, a new, broadly distributed member of the immunoglobulin superfamily, has strong homology with both the immunoglobulin V domain and the beta-chain of major histocompatibility complex class II antigen","volume":"107","author":"Miyauchi","year":"1990","journal-title":"J. Biochem."},{"key":"ref_13","first-page":"434","article-title":"The human tumor cell-derived collagenase stimulatory factor (renamed EMMPRIN) is a member of the immunoglobulin superfamily","volume":"55","author":"Biswas","year":"1995","journal-title":"Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e00283","DOI":"10.1042\/BSR20150256","article-title":"How, with whom and when: An overview of CD147-mediated regulatory networks influencing matrix metalloproteinase activity","volume":"36","author":"Grass","year":"2015","journal-title":"Biosci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Landras, A., Reger de Moura, C., Jouenne, F., Lebbe, C., Menashi, S., and Mourah, S. (2019). CD147 is a promising target of tumor progression and a prognostic biomarker. Cancers, 11.","DOI":"10.3390\/cancers11111803"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"32804","DOI":"10.1038\/srep32804","article-title":"CD147\/EMMPRIN overexpression and prognosis in cancer: A systematic review and meta-analysis","volume":"6","author":"Xin","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1093\/jjco\/hyq098","article-title":"CD147 and VEGF co-expression predicts prognosis in patients with acute myeloid leukemia","volume":"40","author":"Fu","year":"2010","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2286","DOI":"10.1038\/leu.2012.91","article-title":"Increased expression of extracellular matrix metalloproteinase inducer (CD147) in multiple myeloma: Role in regulation of myeloma cell proliferation","volume":"26","author":"Arendt","year":"2012","journal-title":"Leukemia"},{"key":"ref_19","first-page":"1983","article-title":"EMMPRIN (CD 147) is expressed in Hodgkin\u2019s lymphoma and anaplastic large cell lymphoma. An immunohistochemical study of 60 cases","volume":"22","author":"Thorns","year":"2002","journal-title":"Anticancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1002\/path.1518","article-title":"Emmprin, a cell surface inducer of matrix metalloproteinases (MMPs), is expressed in T-cell lymphomas","volume":"202","author":"Nabeshima","year":"2004","journal-title":"J. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/leu.2016.389","article-title":"PKM2 and other key regulators of Warburg effect positively correlate with CD147 (EMMPRIN) gene expression and predict survival in multiple myeloma","volume":"31","author":"Panchabhai","year":"2017","journal-title":"Leukemia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1126\/science.6238408","article-title":"Cyclophilin: A specific cytosolic binding protein for cyclosporin A","volume":"226","author":"Handschumacher","year":"1984","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1186\/gb-2005-6-7-226","article-title":"The cyclophilins","volume":"6","author":"Wang","year":"2005","journal-title":"Genome Biol."},{"key":"ref_24","first-page":"RA221","article-title":"Cyclophilin A: Potential functions and therapeutic target for human cancer","volume":"15","author":"Obchoei","year":"2009","journal-title":"Med. Sci. Monit."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1002\/cncr.21862","article-title":"Cyclophilin A is overexpressed in human pancreatic cancer cells and stimulates cell proliferation through CD147","volume":"106","author":"Li","year":"2006","journal-title":"Cancer"},{"key":"ref_26","first-page":"198","article-title":"Cyclophilin A-EMMPRIN interaction induces invasion of head and neck squamous cell carcinoma","volume":"27","author":"Takahashi","year":"2012","journal-title":"Oncol. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1007\/s13277-014-2691-5","article-title":"Secreted cyclophilin A mediates G1\/S phase transition of cholangiocarcinoma cells via CD147\/ERK1\/2 pathway","volume":"36","author":"Obchoei","year":"2015","journal-title":"Tumour Biol."},{"key":"ref_28","first-page":"7035847","article-title":"Downregulation of CyclophilinA\/CD147 Axis Induces Cell Apoptosis and Inhibits Glioma Aggressiveness","volume":"2020","author":"Xu","year":"2020","journal-title":"BioMed Res. Int."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/nm.3867","article-title":"The Cyclophilin A-CD147 complex promotes the proliferation and homing of multiple myeloma cells","volume":"21","author":"Zhu","year":"2015","journal-title":"Nat. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1111\/j.1600-0625.2010.01138.x","article-title":"A novel xenograft model of cutaneous T-cell lymphoma","volume":"19","author":"Krejsgaard","year":"2010","journal-title":"Exp. Dermatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"318","DOI":"10.4161\/cbt.5.3.2431","article-title":"Biodistribution and localization of iodine-131-labeled metuximab in patients with hepatocellular carcinoma","volume":"5","author":"Zhang","year":"2006","journal-title":"Cancer. Biol. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"dju239","DOI":"10.1093\/jnci\/dju239","article-title":"Randomized trial of [131I] metuximab in treatment of hepatocellular carcinoma after percutaneous radiofrequency ablation","volume":"106","author":"Bian","year":"2014","journal-title":"J. Natl. Cancer. Inst."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4810","DOI":"10.1038\/s41467-020-18444-2","article-title":"Efficacy of anti-CD147 chimeric antigen receptors targeting hepatocellular carcinoma","volume":"11","author":"Tseng","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1089\/gtmb.2014.0067","article-title":"Clinical significance of cyclophilin a expression in esophageal squamous cell carcinoma","volume":"19","author":"Feng","year":"2015","journal-title":"Genet. Test. Mol. Biomark."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Li, H., Jiang, C., Wu, D., Shi, S., Liao, M., Wang, J., Li, Y., and Xu, Z. (2017). The prognostic and clinicopathologic characteristics of CD147 and esophagus cancer: A meta-analysis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0180271"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2637","DOI":"10.3892\/etm.2017.4818","article-title":"Overexpression of CD147 is associated with poor prognosis, tumor cell migration and ERK signaling pathway activation in hepatocellular carcinoma","volume":"14","author":"Xiao","year":"2017","journal-title":"Exp. Ther. Med."},{"key":"ref_37","first-page":"4691","article-title":"High expression level of peptidylprolyl isomerase A is correlated with poor prognosis of liver hepatocellular carcinoma","volume":"18","author":"Wang","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1111\/exd.13022","article-title":"EMMPRIN\/CD147 is an independent prognostic biomarker in cutaneous melanoma","volume":"25","author":"Caudron","year":"2016","journal-title":"Exp. Dermatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1046\/j.1523-1747.2002.01709.x","article-title":"Localization of calcineurin\/NFAT in human skin and psoriasis and inhibition of calcineurin\/NFAT activation in human keratinocytes by cyclosporin A","volume":"118","author":"Grant","year":"2002","journal-title":"J. Investig. Dermatol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Han, J.M., Sohng, J.K., Lee, W.H., Oh, T.J., and Jung, H.J. (2021). Identification of Cyclophilin A as a Potential Anticancer Target of Novel Nargenicin A1 Analog in AGS Gastric Cancer Cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052473"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1111\/j.1600-0560.2007.00924.x","article-title":"A genomic and expression study of AP-1 in primary cutaneous T-cell lymphoma: Evidence for dysregulated expression of JUNB and JUND in MF and SS","volume":"35","author":"Mao","year":"2008","journal-title":"J. Cutan. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.jaad.2013.04.027","article-title":"A comprehensive immunohistochemical approach of AKT\/mTOR pathway and p-STAT3 in mycosis fungoides","volume":"69","author":"Levidou","year":"2013","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1111\/exd.12547","article-title":"In situ assessment of PI3K and PTEN alterations in mycosis fungoides: Correlation with clinicopathological features","volume":"23","author":"Papadavid","year":"2014","journal-title":"Exp. Dermatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1182\/blood-2017-02-768234","article-title":"Genomic analysis of 220 CTCLs identifies a novel recurrent gain-of-function alteration in RLTPR (p.Q575E)","volume":"130","author":"Park","year":"2017","journal-title":"Blood"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/15\/7889\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:34:01Z","timestamp":1760164441000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/15\/7889"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,23]]},"references-count":44,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["ijms22157889"],"URL":"https:\/\/doi.org\/10.3390\/ijms22157889","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,23]]}}}