Tumor microenvironment regulated by carcinoma-associated fibroblasts with different ER-activating abilities

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Carcinoma-associated fibroblasts (CAFs) are associated with tumor progression and metastasis, and are able to activate estrogen receptor (ER) in breast cancer. To elucidate whether the aberrant stromal cells are associated with ER-activation of tumor cells, we examined genetic aberrations of TP53 and PTEN in CAFs. Although various ER-activating abilities were detected in individual CAF, all CAFs maintained wild-type allele. These results suggest that the ER-activating ability of the cells is regulated independently of the aberration of these tumor suppressor genes. To investigate new therapeutic targets in the tumor microenvironment, we studied cytokines produced in co-culture of E10 cells and CAFs with different ER-activating abilities. Several interleukins (ILs) were detected at high-levels in the conditioned media from CAFs with low ER-activating abilities. Further understanding of significance of ILs and CAFs in breast cancer might be important to establish new therapeutic targets.