Lumican expression, localization and antitumor activity in prostate cancer

Lumican expression, localization and antitumor activity in prostate cancer

Autor Coulson-Thomas, Vivien Jane Autor UNIFESP Google Scholar
Coulson-Thomas, Yvette May Autor UNIFESP Google Scholar
Gesteira, Tarsis F. Autor UNIFESP Google Scholar
Andrade de Paula, Claudia A. Autor UNIFESP Google Scholar
Carneiro, Celia R. W. Autor UNIFESP Google Scholar
Ortiz, Valdemar Autor UNIFESP Google Scholar
Toma, Leny Autor UNIFESP Google Scholar
Kao, Winston W. -Y. Google Scholar
Nader, Helena B. Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Univ Cincinnati
Resumo The stromal reaction surrounding tumors leads to the formation of a tumor-specific microenvironment, which may play either a restrictive role or a supportive role in the growth and progression of the tumors. Lumican, a small leucine-rich proteoglycan (SLRP) of the extracellular matrix (ECM), regulates collagen fibrillogenesis. Recently, lumican has also been shown to regulate cell behavior during embryonic development, tissue repair and tumor progression. the role of lumican in cancer varies according to the type of tumor. in this study we analyze the role of lumican in the pathogenesis of prostate cancer both in vivo and in vitro. Overall lumican up-regulation was observed in the primary tumors analyzed through both real-time PCR and immunostaining. the increase in lumican expression was observed in the reactive stroma surrounding prostate primary tumors with fibrotic deposition surrounding the acinar glands. in vitro analysis demonstrated that lumican inhibited both the migration and invasion of metastatic prostate cancer cells isolated from lymph node, bone and brain. Moreover, prostate cancer cells seeded on lumican presented a decrease in the formation of cellular projections, lamellipodia detected by a decreased rearrangement in ZO-1, keratin 8/18, integrin beta 1 and MT1-MMP, and invadopodia detected by disruption of alpha-smooth muscle actin, cortactin and N-WASP. Moreover, a significant increase in prostate cancer cell invasion was observed through the peritoneum of lumican knockout mice, further demonstrating the restrictive role lumican present in the ECM has on prostate cancer invasion. in conclusion, lumican present in the reactive stroma surrounding prostate primary tumors plays a restrictive role on cancer progression, and we therefore postulate that lumican could be a valuable marker in prostate cancer staging. (C) 2013 Elsevier Inc. All rights reserved.
Palavra-chave Lumican
Desmoplasia
Tumor markers
Prostate cancer
Cytoskeleton
Cell migration
Idioma Inglês
Financiador Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
NIH/NEI
Número do financiamento FAPESP: 2007/59801-1
FAPESP: 2010/52426-3
NIH/NEI: EY 011845
Data de publicação 2013-04-15
Publicado em Experimental Cell Research. San Diego: Elsevier Inc, v. 319, n. 7, p. 967-981, 2013.
ISSN 0014-4827 (Sherpa/Romeo, fator de impacto)
Publicador Elsevier B.V.
Extensão 967-981
Fonte http://dx.doi.org/10.1016/j.yexcr.2013.01.023
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000316830100004
Endereço permanente http://repositorio.unifesp.br/handle/11600/36214

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