Lumican expression, localization and antitumor activity in prostate cancer

Autor(es)

Coulson-Thomas, Vivien J. ^{[1, 2]} ; Coulson-Thomas, Yvette M. ^[1] ; Gesteira, Tarsis F. ^[1] ; Andrade de Paula, Claudia A. ^[1] ; Carneiro, Celia R. W. ^[3] ; Ortiz, Valdemar ^[4] ; Toma, Leny ^[1] ; Kao, Winston W. -Y. ^[2] ; Nader, Helena B. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Bioquim, BR-04044020 Sao Paulo - Brazil

^[2] Univ Cincinnati, Edith J Crawley Vis Res Ctr, Coll Med, Dept Ophthalmol, Cincinnati, OH 45267 - USA

^[3] Univ Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, BR-04044020 Sao Paulo - Brazil

^[4] Univ Fed Sao Paulo, Dept Urol, BR-04044020 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Experimental Cell Research; v. 319, n. 7, p. 967-981, APR 15 2013.
• Citações Web of Science: 33

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. (AU)

• Processo FAPESP: 07/59801-1 - Estudo do envolvimento dos proteoglicanos na interacao entre celulas tumorais e estromais na formacao do tumor coloretal e de prostata
• Beneficiário: Leny Toma
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/52426-3 - Espectrometria de massas e de ressonância magnética nuclear na caracterização estrutural de glicosaminoglicanos e polissacarídeos complexos de invertebrados e algas
• Beneficiário: Helena Bonciani Nader
• Modalidade de apoio: Auxílio à Pesquisa - Regular