Infiltrating T cells promote renal cell carcinoma (RCC) progression via altering the estrogen receptor ?-DAB2IP signals.

ABSTRACT: Previous studies indicated the T cells, one of the most common types of immune cells existing in the microenvironment of renal cell carcinoma (RCC), may influence the progression of RCC. The potential linkage of T cells and the estrogen receptor beta (ER?), a key player to impact RCC progression, however, remains unclear. Our results demonstrate that RCC cells can recruit more T cells than non-malignant kidney cells. Using an in vitro matrigel invasion system, we found infiltrating T cells could promote RCC cells invasion via increasing ER? expression and transcriptional activity. Mechanism dissection suggested that co-culturing T cells with RCC cells released more T cell attraction factors, including IFN-?, CCL3 and CCL5, suggesting a positive regulatory feed-back mechanism. Meanwhile, infiltrating T cells may also promote RCC cell invasion via increased ER? and decreased DAB2IP expressions, and knocking down DAB2IP can then reverse the T cells-promoted RCC cell invasion. Together, our results suggest that infiltrating T cells may promote RCC cell invasion via increasing the RCC cell ER? expression to inhibit the tumor suppressor DAB2IP signals. Further mechanism dissection showed that co-culturing T cells with RCC cells could produce more IGF-1 and FGF-7, which may enhance the ER? transcriptional activity. The newly identified relationship between infiltrating T cells/ER?/DAB2IP signals may provide a novel therapeutic target in the development of agents against RCC.

SUBMITTER: Yeh CR 

PROVIDER: S-EPMC4792561 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature