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Blocking stanniocalcin 2 reduces sunitinib resistance in clear cell renal cell carcinoma

Zhen-Qian Qin, Kong-Dong Li, He-Zhen Chu, Xue-Feng Yuan, Hai-Feng Shi,  Jie Gu,  Yi-Min Xie

Abstract:

Stanniocalcin 2 (STC2) has been identified as a prognostic marker in renal cell carcinoma. However, the role of STC2 in renal cell carcinoma is still unclear. In this study, we investigated the relationship between high expression of STC2 and sunitinib resistance in cells and the underlying mechanism. Through GEPIA platform analysis based on TCGA database, it showed that the expression of STC2 in kidney renal clear cell carcinoma (KIRC) was significantly higher than that in the normal population. Real-time quantitative PCR and western blotting detected significantly higher expression levels of STC2 in clear cell renal cell carcinoma (ccRCC) cells than that in normal renal cells. Enzyme-linked immunosorbent assay (ELISA) determined whether there is a high secretion of STC2 in ccRCC cells. The sunitinib resistance could be significantly reduced by STC2 neutralizing antibody but aggravated by the addition of recombinant human STC2 in ccRCC cells. Sunitinib suppressed STC2 expression and secretion, destroyed lysosomal acidic pH, and accumulated in the cells. However, STC2 neutralizing antibody can reduce the accumulation of sunitinib in cells to improve the inhibitory efficiency of sunitinib on cell proliferation. This study suggested STC2 could serve as a potential novel target for the treatment of ccRCC, anti-STC2 antibody might be an option of immunotherapy in the future.

Received date: 08/23/2021

Accepted date: 11/08/2021

Ahead of print publish date: 12/10/2021

Issue: 1/2022

Volume: 69

Pages: 145 — 154

Keywords: stanniocalcin 2, clear cell renal cell carcinoma, sunitinib, drug resistance

Supplementary files:
N1206 Suppl FigS1-TE1.tif
N1206 Suppl FigS2-TE1.tif
N1206 Supplementary Figure Legends.doc

DOI: 10.4149/neo_2021_210823N1206

Pubmed

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