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- W2590996474 abstract "488 Background: Tumor microenvironment is a complex network of multiple cell types, paracrine and endocrine signaling molecules, ECM and physical factors, which orchestrate the fate of tumor progression. In the field of ccRCC little attention has been paid to non-immunologic factors in tumor niche. Objectives of this study include the analysis of hypoxia, triiodothyronine (T3), insulin, insulin-like growth factor-1 and -2 impact on ccRCC cells. The effect of above mentioned tumor niche factors on TKI activity on ccRCC cells was to be quantified. The study was initiated as ccRCC cells are known to harbor disrupted hypoxia response and TRbeta (TRβ) - T3 receptor - functions as a tumor suppressor with tissue hypothyroidism involved in maintaining a proliferative advantage, whereas hypothyroidisms was defined as biomarker of sunitinib treatment efficacy. Moreover obesity and diabetes (DM2) are considered risk factors for ccRCC and high IGF-I expression is associated with poor long-term patient survival. This research aims to find molecular background for clinically relevant observations. Methods: ccRCC cells from primary and metastatic tumors (ATCC, MSK collections) along with cancer progenitor cells (CD133+) were cultured in normoxic or hypoxic conditions; in defined media supplemented with T3, IN, IGF, TRβ inhibitor and TKIs (sunitinib, axitinib). Cell proliferation was evaluated using AlamarBlue and MTT. Colony formation potential was evaluated. TRβ gene expression was measured with RealTime-RT PCR and sequenced under standard protocol. Normal kidney proximal tube cells were used as negative control. Results: ccRCC TKI responsiveness is limited by hypoxia, at the same time tumor cell proliferation may be promoted by T3, IN and IGF. Colony formation potential of ccRCC cells under TKI treatment in hypoxic conditions is downregulated. Conclusions: Multiple micro-environmental factors modify the proliferation and/or differentiation of ccRCC cell populations. Understanding the complex molecular feedback loops between cancer cells and the surrounding microenvironment should aid the identification of novel targets for improving TKIs clinical management." @default.
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- W2590996474 date "2014-02-01" @default.
- W2590996474 modified "2023-09-26" @default.
- W2590996474 title "The regulation of clear cell renal cancer cells proliferation and tyrosine kinase inhibitors responsiveness by tumor micro-environmental factors." @default.
- W2590996474 doi "https://doi.org/10.1200/jco.2014.32.4_suppl.488" @default.
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