Vitamin D3 modulation of plasminogen activator inhibitor type-1 in human breast carcinomas under organ culture |
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Authors: | Edson?Mantovani?Barbosa,Sueli?Nonogaki,Maria?Lucia?Hirata?Katayama,Maria?Aparecida?Azevedo?Koike?Folgueira,Venancio?Ferreira?Avancini?Alves,Maria?Mitzi?Brentani author-information" > author-information__contact u-icon-before" > mailto:mbrentani@lim.fm.usp.br" title=" mbrentani@lim.fm.usp.br" itemprop=" email" data-track=" click" data-track-action=" Email author" data-track-label=" " >Email author |
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Affiliation: | (1) Instituto Brasileiro do Controle do Cancer, Avenida Alcântara Machado 2576, CEP 03102-002 São Paulo, SP, Brasil;(2) Divisão de Patologia, Laboratório de Imunohistoquímica, Instituto Adolpho Lutz, Av. Dr. Arnaldo 355, 7º sandar, CEP 01246-902 São PauloSP, Brasil;(3) Departamento de Radiologia, Faculdade de Medicina da USP, Disciplina de Oncologia, Av. Dr. Arnaldo 455, 4º andar, Sala 4112, CEP 01246-903 São Paulo, Brasil |
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Abstract: | Urokinase plasminogen activator (uPA), its cell-bound receptor (uPAR) and its main inhibitor plasminogen activator type 1 (PAI-1) are present primarily in stromal cells in invasive breast carcinoma. The purpose of this study was to investigate the regulation by 1,25 dihydroxyvitamin-D3 (VD3) of these invasion-associated markers expressed in breast cancer tumors under organ culture, which preserves the interacting network of tumor and stromal cells. Breast carcinoma slices (30 cases), obtained using the Krumdieck tissue slicer, cultured for 48 h in the presence or absence of 100 nM vitamin D3, were embedded in formalin-fixed paraffin. uPA, uPAR, PAI-1 and VD3 receptor (VDR) were analyzed by immunohistochemistry, and their expression, detected in tumor cells and fibroblasts of the specimens, was not statistically changed by culture conditions. The proportion of cases expressing uPA, uPAR and PAI-1 was not affected by VD3 in epithelial cells, but the fraction of cases displaying strong PAI-1 reactivity in fibroblasts was reduced (P=0.016) compared with control slices. Fibroblasts isolated from invasive ductal carcinomas and from normal breast tissues expressed higher VDR mRNA levels than epithelial cells. In cultured tumor fibroblasts, PAI-1 immunostaining and mRNA levels were reduced by VD3-limiting fibroblast contribution to invasion. |
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Keywords: | Breast cancer Calcitriol Fibroblasts PAI-1 Organ culture |
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