Infiltrating T cells promote renal cell carcinoma (RCC) progression via altering the estrogen receptor β-DAB2IP signals
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Chiuan-Ren Yeh1,2, Zheng-Yu Ou1, Guang-Qian Xiao2, Elizabeth Guancial3, Shuyuan Yeh1,2
1Department of Urology, University of Rochester Medical Center, Rochester, NY 14642, USA
2Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642, USA
3Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA
Shuyuan Yeh, e-mail: [email protected]
Keywords: ERβ, RCC, metastasis, DAB2IP, CD4+ T cells
Received: August 12, 2015 Accepted: October 13, 2015 Published: November 17, 2015
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 (ERβ), 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 ERβ expression and transcriptional activity. Mechanism dissection suggested that co-culturing T cells with RCC cells released more T cell attraction factors, including IFN-γ, CCL3 and CCL5, suggesting a positive regulatory feed-back mechanism. Meanwhile, infiltrating T cells may also promote RCC cell invasion via increased ERβ 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 ERβ 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 ERβ transcriptional activity. The newly identified relationship between infiltrating T cells/ERβ/DAB2IP signals may provide a novel therapeutic target in the development of agents against RCC.
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