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GPR30 knockdown weakens the capacity of CAF in promoting prostate cancer cell invasion via reducing macrophage infiltration and M2 polarization
Author(s) -
Zhang Ran,
Zong Jiaojiao,
Peng Yanfei,
Shi Jiandang,
Du Xiaoling,
Liu Haitao,
Shen Yongmei,
Cao Jiasong,
Jia Bona,
Liu Feng,
Zhang Ju
Publication year - 2021
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.29938
Subject(s) - tumor microenvironment , stromal cell , prostate cancer , cancer research , cancer associated fibroblasts , gper , chemokine , macrophage polarization , microbiology and biotechnology , metastasis , inflammation , immune system , chemistry , prostate , macrophage , biology , immunology , medicine , estrogen receptor , cancer , breast cancer , in vitro , biochemistry
Cancer‐associated fibroblasts (CAFs) can promote the development and metastasis of prostate cancer partly by mediating tumor‐associated inflammation. An increasing amount of studies have focused on the functional interactions between CAFs and immune cells in the tumor microenvironment (TME). We previously reported that G protein‐coupled receptor 30 (GPR30) was highly expressed in prostate CAFs and plays a crucial role in prostate stromal cell activation. However, the effect and underlying mechanism of GPR30 expression in prostate CAFs affecting the interaction between CAFs and tumor‐associated macrophages (TAMs) need further elucidation. Here, we found that, compared with CAF‐shControl, CAF‐shGPR30 inhibited macrophage migration through transwell migration assays, which should be attributed to the decreased expression of C‐X‐C motif chemokine ligand 12 (CXCL12). In addition, macrophages treated with a culture medium of CAF‐shGPR30 exhibited attenuated M2 polarization with downregulated M2‐like markers expression. Moreover, macrophages stimulated with a culture medium of CAF‐shGPR30 were less efficient in promoting activation of fibroblast cells and invasion of PCa cells. Finally, cocultured CAF‐shGPR30 and macrophages suppressed PCa cell invasion compared to cocultured CAF‐shControl and macrophages by decreasing interleukin‐6 (IL‐6) secretion, and this effect could be abrogated with rescue expression of IL‐6. Our results pinpoint the function of GPR30 in prostate CAFs on regulating the CAF‐TAM interaction in the TME and provide new insights into PCa therapies via regulating TME.