{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T18:16:28Z","timestamp":1777486588064,"version":"3.51.4"},"reference-count":60,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T00:00:00Z","timestamp":1733270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PIAP Jovem Call","award":["001\/2017 IGM\/FIOCRUZ"],"award-info":[{"award-number":["001\/2017 IGM\/FIOCRUZ"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: The present study investigates VKINE, a bioactive proteolytic fragment of the proteoglycan VCAN, as a novel and significant element in the tumor extracellular matrix (ECM). Although VKINE has been recognized for its immunomodulatory potential in certain tumor types, its impact on ECM degradation and prognostic implications remains poorly understood. Objectives: This study aimed to evaluate VCAN proteolysis and its association with ADAMTS enzymes involved in extracellular matrix remodeling in spontaneous canine mammary gland cancer. Methods: The expression levels of VKINE, ADAMTS enzymes, and collagen fibers were comparatively analyzed in situ and in invasive areas of carcinoma in mixed tumor (CMT) and carcinosarcoma (CSS) with different prognoses. Results: VKINE was notably expressed in the stroma adjacent to the invasion areas in CMT, whereas ADAMTS-15 was identified as the enzyme associated with VCAN proteolysis. Inverse correlations were observed between type III collagen and VCAN expression in in situ areas. Conclusions: Our findings suggest that VKINE and ADAMTS-15 play crucial roles in the tumor microenvironment, influencing invasiveness and type III collagen deposition. This study contributes to a better understanding of the dynamics within the ECM, paving the way for potential new tools in diagnosing and treating human and canine mammary tumors.<\/jats:p>","DOI":"10.3390\/cancers16234057","type":"journal-article","created":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T04:47:22Z","timestamp":1733287642000},"page":"4057","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Versican Proteolysis by ADAMTS: Understanding Versikine Expression in Canine Spontaneous Mammary Carcinomas"],"prefix":"10.3390","volume":"16","author":[{"given":"Maria Carolina","family":"Souza","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Pathology, Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation, 121 Rua Waldemar Falc\u00e3o, Salvador 40296-710, BA, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Nunes","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Pathology, Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation, 121 Rua Waldemar Falc\u00e3o, Salvador 40296-710, BA, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4768-218X","authenticated-orcid":false,"given":"Samantha Hellen Santos","family":"Figuer\u00eado","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Pathology, Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation, 121 Rua Waldemar Falc\u00e3o, Salvador 40296-710, BA, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno Sousa","family":"de Almeida","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Pathology, Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation, 121 Rua Waldemar Falc\u00e3o, Salvador 40296-710, BA, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isac Patrick Concei\u00e7\u00e3o","family":"Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Pathology, Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation, 121 Rua Waldemar Falc\u00e3o, Salvador 40296-710, BA, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5650-6743","authenticated-orcid":false,"given":"Geovanni Dantas","family":"Cassali","sequence":"additional","affiliation":[{"name":"Comparative Pathology Laboratory, Department of Pathology, Institute of Biological Sciences, Federal University of Minas Gerais, 6627 Av. Pres. Ant\u00f4nio Carlos, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3071-6339","authenticated-orcid":false,"given":"S\u00e9rgio Marcos","family":"Arruda","sequence":"additional","affiliation":[{"name":"Advanced Public Health Laboratory, Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation, 121 Rua Waldemar Falc\u00e3o, Salvador 40296-710, BA, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0074-9789","authenticated-orcid":false,"given":"Thiago Marconi de Souza","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Clinical Research Laboratory, Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation, 121 Rua Waldemar Falc\u00e3o, Salvador 40296-710, BA, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9879-7999","authenticated-orcid":false,"given":"Alessandra","family":"Estrela-Lima","sequence":"additional","affiliation":[{"name":"Research Center on Mammary Oncology NPqOM\/HOSPMEV, Federal University of Bahia, Salvador 40170-110, BA, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2087-1690","authenticated-orcid":false,"given":"Karine Ara\u00fajo","family":"Damasceno","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Pathology, Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation, 121 Rua Waldemar Falc\u00e3o, Salvador 40296-710, BA, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/35077241","article-title":"The Microenvironment of the Tumour\u2013Host Interface","volume":"411","author":"Liotta","year":"2001","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1002\/ijc.24812","article-title":"Versican Overexpression in Human Breast Cancer Lesions: Known and New Isoforms for Stromal Tumor Targeting","volume":"126","author":"Kischel","year":"2010","journal-title":"Int. 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