Vitamin D3 modulation of plasminogen activator inhibitor type-1 in human breast carcinomas under organ culture.
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.
Barbosa
Edson Mantovani
EM
Instituto Brasileiro do Controle do Cancer, Avenida Alcântara Machado 2576, CEP 03102-002, São Paulo, SP, Brasil.
Nonogaki
Sueli
S
Katayama
Maria Lucia Hirata
ML
Folgueira
Maria Aparecida Azevedo Koike
MA
Alves
Venâncio Ferreira Avancini
VF
Brentani
Maria Mitzi
MM
D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000378:metabolism*; D044584:Carcinoma, Ductal / Q000378:metabolism*; D045744:Cell Line, Tumor; D002762:Cholecalciferol / Q000378:metabolism* / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D009924:Organ Culture Techniques; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D018167:Receptors, Calcitriol / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D002762:Cholecalciferol; D014568:Urokinase-Type Plasminogen Activator