Reciprocal changes in gene expression profiles of cocultured breast epithelial cells and primary fibroblasts

Author(s):Show less -

Rozenchan, Patricia Bortman ^[1] ; Carraro, Dirce Maria ^[2] ; Brentani, Helena ^[2] ; de Carvalho Mota, Louise Danielle ^[2] ; Bastos, Elen Pereira ^[1] ; Napolitano e Ferreira, Elisa ^[2] ; Torre, Cesar H. ^[2] ; Hirata Katayama, Maria Lucia ^[1] ; Roela, Rosimeire Aparecida ^[1] ; Lyra, Eduardo C. ^[3] ; Soares, Fernando Augusto ^[2] ; Azevedo Koike Folgueira, Maria Aparecida ^[1] ; Guedes Sampaio Goes, Joao Carlos ^[3] ; Brentani, Maria Mitzi ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Med, Dept Radiol, Disciplina Oncol, BR-01246903 Sao Paulo - Brazil

^[2] Hosp AC Camargo Fund Antonio Prudente, Ctr Ensino & Pesquisa, BR-01509900 Sao Paulo - Brazil

^[3] Inst Brasileiro Controle Canc, BR-03102002 Sao Paulo - Brazil

• Document type: Journal article
• Source: International Journal of Cancer; v. 125, n. 12, p. 2767-2777, DEC 15 2009.
• Web of Science Citations: 41

Abstract

The importance of epithelial-stroma interaction in normal breast development and tumor progression has been recognized. To identify genes that were regulated by these reciprocal interactions, we cocultured a nonmalignant (MCF10A) and a breast cancer derived (MDA-MB231) basal cell lines, with fibroblasts isolated from breast benign-disease adjacent tissues (NAF) or with carcinoma-associated fibroblasts (CAF), in a transwell system. Gene expression profiles of each coculture pair were compared with the correspondent monocultures, using a customized microarray. Contrariwise to large alterations in epithelial cells genomic profiles, fibroblasts were less affected. In MDA-MB231 highly represented genes downregulated by CAF derived factors coded for proteins important for the specificity of vectorial transport between ER and golgi, possibly affecting cell polarity whereas the response of MCF10A comprised an induction of genes coding for stress responsive proteins, representing a prosurvival effect. While NAF downregulated genes encoding proteins associated to glycolipid and fatty acid biosynthesis in MDA-MB231, potentially affecting membrane biogenesis, in MCF10A, genes critical for growth control and adhesion were altered. NAFs responded to coculture with MDA-MB231 by a decrease in the expression of genes induced by TGF beta 1 and associated to motility. However, there was little change in NAFs gene expression profile influenced by MCF10A. CAFs responded to the presence of both epithelial cells inducing genes implicated in cell proliferation. Our data indicate that interactions between breast fibroblasts and basal epithelial cells resulted in alterations in the genomic profiles of both cell types which may help to clarify some aspects of this heterotypic signaling. (C) 2009 UICC (AU)

• FAPESP's process: 04/04607-8 - Heterotypic signaling between epithelial tumor cells and fibroblasts in carcinoma of the breast
• Grantee: Maria Mitzi Brentani
• Support Opportunities: Research Projects - Thematic Grants