{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T10:51:48Z","timestamp":1762080708620,"version":"build-2065373602"},"reference-count":34,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T00:00:00Z","timestamp":1670976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["UID\/AGR\/04129\/2020","PTDC\/BAA-AGR\/28608\/2017","PTDC\/OCE-ETA\/4836\/2021","SFRH\/BD\/132832\/2017","SFRH\/BD\/139138\/2018"],"award-info":[{"award-number":["UID\/AGR\/04129\/2020","PTDC\/BAA-AGR\/28608\/2017","PTDC\/OCE-ETA\/4836\/2021","SFRH\/BD\/132832\/2017","SFRH\/BD\/139138\/2018"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Matrix metalloproteinases (MMPs) are proteolytic enzymes that play a crucial role in tumor microenvironment remodeling, contributing to inflammatory and angiogenic processes, and ultimately promoting tumor maintenance and progression. Several studies on bioactive polypeptides isolated from legumes have shown anti-migratory, anti-MMPs, and anti-tumor effects, potentially constituting novel strategies for both the prevention and progression of cancer. In this work, we investigated the anti-tumor role of deflamin, a protein oligomer isolated from white lupine seeds (Lupinus albus) reported to inhibit MMP-9 and cell migration in colorectal cancer (CRC) cell lines. We found that deflamin exerts an inhibitory effect on tumor growth and metastasis formation, contributing to increased tumor apoptosis in the xenotransplanted zebrafish larvae model. Furthermore, deflamin resulted not only in a significant reduction in MMP-2 and MMP-9 activity but also in impaired cancer cell migration and invasion in vitro. Using the xenograft zebrafish model, we observed that deflamin inhibits collagen degradation and angiogenesis in the tumor microenvironment in vivo. Overall, our work reveals the potential of deflamin as an agent against CRC development and progression.<\/jats:p>","DOI":"10.3390\/cancers14246182","type":"journal-article","created":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T03:01:51Z","timestamp":1671073311000},"page":"6182","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Therapeutic Potential of Deflamin against Colorectal Cancer Development and Progression"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3896-8706","authenticated-orcid":false,"given":"Sara","family":"Silva","sequence":"first","affiliation":[{"name":"Instituto de Medicina Molecular\u2014Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0642-1979","authenticated-orcid":false,"given":"Ana","family":"Cavaco","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular\u2014Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2024-4323","authenticated-orcid":false,"given":"Bianca","family":"Basso","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular\u2014Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8835-852X","authenticated-orcid":false,"given":"Joana","family":"Mota","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Lus\u00f3fona University, 1749-024 Lisbon, Portugal"},{"name":"LEAF\u2014Linking Landscape, Environment, Agriculture and Food, Instituto Superior de Agronomia, Universidade de Lisboa, Tapada da Ajuda, 1349-017 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2047-2369","authenticated-orcid":false,"given":"Raquel","family":"Cruz-Duarte","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular\u2014Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal"}]},{"given":"Miguel","family":"Costa","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular\u2014Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal"}]},{"given":"Lara","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular\u2014Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8251-6286","authenticated-orcid":false,"given":"Ana","family":"Lima","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Lus\u00f3fona University, 1749-024 Lisbon, Portugal"},{"name":"LEAF\u2014Linking Landscape, Environment, Agriculture and Food, Instituto Superior de Agronomia, Universidade de Lisboa, Tapada da Ajuda, 1349-017 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4782-7318","authenticated-orcid":false,"given":"Luis","family":"Costa","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular\u2014Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal"},{"name":"Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, 1649-028 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5027-7564","authenticated-orcid":false,"given":"Ricardo","family":"Ferreira","sequence":"additional","affiliation":[{"name":"LEAF\u2014Linking Landscape, Environment, Agriculture and Food, Instituto Superior de Agronomia, Universidade de Lisboa, Tapada da Ajuda, 1349-017 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0429-9380","authenticated-orcid":false,"given":"Marta","family":"Martins","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular\u2014Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","first-page":"28","article-title":"Molecular Principles of Metastasis: A Hallmark of Cancer Revisited. Signal Transduct","volume":"5","author":"Fares","year":"2020","journal-title":"Target. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/j.1742-4658.2010.07919.x","article-title":"Roles of Matrix Metalloproteinases in Cancer Progression and Their Pharmacological Targeting","volume":"278","author":"Gialeli","year":"2011","journal-title":"FEBS J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2387","DOI":"10.1126\/science.1067100","article-title":"Matrisian Matrix Metalloproteinase Inhibitors and Cancer\u2014Trials and Tribulations","volume":"295","author":"Coussens","year":"2002","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/1477-7819-12-24","article-title":"Matrix Metalloproteinase-9 Overexpression Is Closely Related to Poor Prognosis in Patients with Colon Cancer","volume":"12","author":"Yang","year":"2014","journal-title":"World J. Surg. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1023\/A:1006573417179","article-title":"The Matrix Metalloproteinase Inhibitor Batimastat Inhibits Angiogenesis in Liver Metastases of B16F1 Melanoma Cells","volume":"17","author":"Wylie","year":"1999","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_7","first-page":"985","article-title":"Batimastat, a Synthetic Inhibitor of Matrix Metalloproteinases, Potentiates the Antitumor Activity of Cisplatin in Ovarian Carcinoma Xenografts","volume":"4","author":"Giavazzi","year":"1998","journal-title":"Clin. Cancer Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1038\/sj.bjc.6600446","article-title":"A Double-Blind Placebo-Controlled, Randomised Study Comparing Gemcitabine and Marimastat with Gemcitabine and Placebo as First Line Therapy in Patients with Advanced Pancreatic Cancer","volume":"87","author":"Bramhall","year":"2002","journal-title":"Br. J. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.ygyno.2005.12.020","article-title":"A Phase III Randomized Trial of BAY 12-9566 (Tanomastat) as Maintenance Therapy in Patients with Advanced Ovarian Cancer Responsive to Primary Surgery and Paclitaxel\/Platinum Containing Chemotherapy: A National Cancer Institute of Canada Clinical Trials Group Study","volume":"102","author":"Hirte","year":"2006","journal-title":"Gynecol. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4631","DOI":"10.1200\/JCO.2004.08.054","article-title":"Randomized Phase III Trial of Marimastat versus Placebo in Patients with Metastatic Breast Cancer Who Have Responding or Stable Disease after First-Line Chemotherapy: Eastern Cooperative Oncology Group Trial E2196","volume":"22","author":"Sparano","year":"2004","journal-title":"J. Clin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3657","DOI":"10.4161\/cc.8.22.9956","article-title":"Protective Roles of Matrix Metalloproteinases: From Mouse Models to Human Cancer","volume":"8","author":"Palavalli","year":"2009","journal-title":"Cell Cycle"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.canlet.2009.04.037","article-title":"Curcumin Inhibits the Migration and Invasion of Human A549 Lung Cancer Cells through the Inhibition of Matrix Metalloproteinase-2 and -9 and Vascular Endothelial Growth Factor (VEGF)","volume":"285","author":"Lin","year":"2009","journal-title":"Cancer Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/sj.pcan.4500856","article-title":"The Effects of Curcumin on the Invasiveness of Prostate Cancer in vitro and in vivo","volume":"9","author":"Hong","year":"2006","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.jnutbio.2007.12.003","article-title":"Curcumin, Demethoxycurcumin and Bisdemethoxycurcumin Differentially Inhibit Cancer Cell Invasion through the down-Regulation of MMPs and UPA","volume":"20","author":"Yodkeeree","year":"2009","journal-title":"J. Nutr. Biochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.jnutbio.2007.03.003","article-title":"Resveratrol Inhibits Heregulin-\u03921-Mediated Matrix Metalloproteinase-9 Expression and Cell Invasion in Human Breast Cancer Cells","volume":"19","author":"Tang","year":"2008","journal-title":"J. Nutr. Biochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.abb.2012.05.003","article-title":"Mediterranean Diet Polyphenols Reduce Inflammatory Angiogenesis through MMP-9 and COX-2 Inhibition in Human Vascular Endothelial Cells: A Potentially Protective Mechanism in Atherosclerotic Vascular Disease and Cancer","volume":"527","author":"Scoditti","year":"2012","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_17","first-page":"4945","article-title":"Suppression of 7,12-Dimethylbenz(a)Anthracene-Induced Mammary Carcinogenesis in Rats by Resveratrol: Role of Nuclear Factor-\u039aB, Cyclooxygenase 2, and Matrix Metalloprotease 9","volume":"62","author":"Banerjee","year":"2002","journal-title":"Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1207\/S15327914NC441_8","article-title":"Consumption of Black Beans and Navy Beans (Phaseolus vulgaris) Reduced Azoxymethane-Induced Colon Cancer in Rats","volume":"44","author":"Bennink","year":"2002","journal-title":"Nutr. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1007\/s10552-009-9406-z","article-title":"Legume Intake and the Risk of Cancer: A Multisite Case-Control Study in Uruguay","volume":"20","author":"Aune","year":"2009","journal-title":"Cancer Causes Control"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Mota, J., Figueira, M.E., Ferreira, R.B., and Lima, A. (2021). An Up-Scalable and Cost-Effective Methodology for Isolating a Polypeptide Matrix Metalloproteinase-9 Inhibitor from Lupinus albus Seeds. Foods, 10.","DOI":"10.3390\/foods10071663"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Mota, J., Direito, R., Rocha, J., Fernandes, J., Sepodes, B., Figueira, M.E., Raymundo, A., Lima, A., and Ferreira, R.B. (2021). Lupinus albus Protein Components Inhibit MMP-2 and MMP-9 Gelatinolytic Activity in vitro and in vivo. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413286"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Mota, J., Lima, A., Ferreira, R.B., and Raymundo, A. (2021). Technological Potential of a Lupin Protein Concentrate as a Nutraceutical Delivery System in Baked Cookies. Foods, 10.","DOI":"10.3390\/foods10081929"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.foodchem.2015.10.063","article-title":"Legume Seeds and Colorectal Cancer Revisited: Protease Inhibitors Reduce MMP-9 Activity and Colon Cancer Cell Migration","volume":"197","author":"Lima","year":"2016","journal-title":"Food Chem."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Mota, J., Casimiro, S., Fernandes, J., Hartmann, R.M., Schemitt, E., Picada, J., Costa, L., Marroni, N., Raymundo, A., and Lima, A. (2022). Lupin Protein Concentrate as a Novel Functional Food Additive That Can Reduce Colitis-Induced Inflammation and Oxidative Stress. Nutrients, 14.","DOI":"10.3390\/nu14102102"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Cavaco, A.C.M., Rezaei, M., Caliandro, M.F., Lima, A.M., Stehling, M., Dhayat, S.A., Haier, J., Brakebusch, C., and Eble, J.A. (2019). The Interaction between Laminin-332 and A3\u03b21 Integrin Determines Differentiation and Maintenance of Cafs, and Supports Invasion of Pancreatic Duct Adenocarcinoma Cells. Cancers, 11.","DOI":"10.3390\/cancers11010014"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e20253","DOI":"10.7554\/eLife.20253","article-title":"Radial Glia Regulate Vascular Patterning around the Developing Spinal Cord","volume":"5","author":"Matsuoka","year":"2016","journal-title":"Elife"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"E8234","DOI":"10.1073\/pnas.1618389114","article-title":"Single-Cell Functional and Chemosensitive Profiling of Combinatorial Colorectal Therapy in Zebrafish Xenografts","volume":"114","author":"Fior","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Okada, Y. (2017). Proteinases and Matrix Degradation, Elsevier Inc.. [10th ed.].","DOI":"10.1016\/B978-0-323-31696-5.00008-5"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.3389\/fonc.2019.01370","article-title":"Role of Matrix Metalloproteinases in Angiogenesis and Cancer","volume":"9","author":"Arreola","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"14767","DOI":"10.1073\/pnas.1209721109","article-title":"Targeting Collagen Strands by Photo-Triggered Triple-Helix Hybridization","volume":"109","author":"Li","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s42826-021-00103-2","article-title":"Transgenic Fluorescent Zebrafish Lines That Have Revolutionized Biomedical Research","volume":"37","author":"Choe","year":"2021","journal-title":"Lab. Anim. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"222","DOI":"10.3109\/10409238.2013.770819","article-title":"Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9): The next decade","volume":"48","author":"Vandooren","year":"2013","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1038\/nrd4627","article-title":"Zebrafish as Tools for Drug Discovery","volume":"14","author":"MacRae","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Augoff, K., Hryniewicz-Jankowska, A., Tabola, R., and Stach, K. (2022). MMP9: A Tough Target for Targeted Therapy for Cancer. Cancers, 14.","DOI":"10.3390\/cancers14071847"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/24\/6182\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:41:29Z","timestamp":1760146889000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/24\/6182"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,14]]},"references-count":34,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["cancers14246182"],"URL":"https:\/\/doi.org\/10.3390\/cancers14246182","relation":{},"ISSN":["2072-6694"],"issn-type":[{"type":"electronic","value":"2072-6694"}],"subject":[],"published":{"date-parts":[[2022,12,14]]}}}