title: Infiltrating T cells promote renal cell carcinoma (RCC) progression via altering the estrogen receptor β-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 (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.
authors.affiliation: Department of Urology, University of Rochester Medical Center, Rochester, NY 14642, USA.|Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Chiuan-Ren
authors.initials: CR
authors.lastname: Yeh
authors.affiliation: Department of Urology, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Zheng-Yu
authors.initials: ZY
authors.lastname: Ou
authors.affiliation: Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Guang-Qian
authors.initials: GQ
authors.lastname: Xiao
authors.affiliation: Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Guancial
authors.affiliation: Department of Urology, University of Rochester Medical Center, Rochester, NY 14642, USA.|Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Yeh
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D054405:Chemokine CCL3 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D018920:Coculture Techniques; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D051523:Fibroblast Growth Factor 7 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007680:Kidney Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism*; D019899:Paracrine Communication; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014162:Transfection; D059016:Tumor Microenvironment; D020703:ras GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C515429:CCL3 protein, human; C483024:CCL5 protein, human; D054405:Chemokine CCL3; D018946:Chemokine CCL5; C462952:DAB2IP protein, human; C000600034:ESR2 protein, human; D047629:Estrogen Receptor beta; C496453:FGF7 protein, human; C573415:IFNG protein, human; C583557:IGF1 protein, human; D020703:ras GTPase-Activating Proteins; D051523:Fibroblast Growth Factor 7; D007334:Insulin-Like Growth Factor I; D007371:Interferon-gamma
keywords: CD4+ T cells; DAB2IP; ERβ; RCC; metastasis