PMID- 33938030 OWN - NLM STAT- Publisher LR - 20240222 IS - 1097-4644 (Electronic) IS - 0730-2312 (Linking) DP - 2021 May 3 TI - GPR30 knockdown weakens the capacity of CAF in promoting prostate cancer cell invasion via reducing macrophage infiltration and M2 polarization. LID - 10.1002/jcb.29938 [doi] AB - 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. CI - (c) 2021 Wiley Periodicals LLC. FAU - Zhang, Ran AU - Zhang R AUID- ORCID: 0000-0002-5036-7121 AD - Department of Biochemistry and Molecular Biology, College of Life Sciences, Bioactive Materials Key Lab of Ministry of Education, Nankai University, Tianjin, China. AD - Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China. FAU - Zong, Jiaojiao AU - Zong J AD - Department of Biochemistry and Molecular Biology, College of Life Sciences, Bioactive Materials Key Lab of Ministry of Education, Nankai University, Tianjin, China. FAU - Peng, Yanfei AU - Peng Y AD - School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. FAU - Shi, Jiandang AU - Shi J AD - Department of Biochemistry and Molecular Biology, College of Life Sciences, Bioactive Materials Key Lab of Ministry of Education, Nankai University, Tianjin, China. FAU - Du, Xiaoling AU - Du X AD - Department of Biochemistry and Molecular Biology, College of Life Sciences, Bioactive Materials Key Lab of Ministry of Education, Nankai University, Tianjin, China. FAU - Liu, Haitao AU - Liu H AD - Shanghai First People's Hospital Shanghai Jiaotong University, Shanghai, China. FAU - Shen, Yongmei AU - Shen Y AD - Department of Biochemistry and Molecular Biology, College of Life Sciences, Bioactive Materials Key Lab of Ministry of Education, Nankai University, Tianjin, China. FAU - Cao, Jiasong AU - Cao J AD - Department of Biochemistry and Molecular Biology, College of Life Sciences, Bioactive Materials Key Lab of Ministry of Education, Nankai University, Tianjin, China. FAU - Jia, Bona AU - Jia B AD - Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Medical University, Tianjin, China. FAU - Liu, Feng AU - Liu F AD - Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Biomedical Sciences, Shandong University, Jinan, Shandong, China. FAU - Zhang, Ju AU - Zhang J AD - Department of Biochemistry and Molecular Biology, College of Life Sciences, Bioactive Materials Key Lab of Ministry of Education, Nankai University, Tianjin, China. LA - eng GR - 81672527/National Natural Science Foundation of China/ GR - 81872087/National Natural Science Foundation of China/ PT - Journal Article DEP - 20210503 PL - United States TA - J Cell Biochem JT - Journal of cellular biochemistry JID - 8205768 SB - IM OTO - NOTNLM OT - G protein-coupled receptor 30 OT - cancer-associated fibroblasts OT - prostate cancer OT - tumor-associated macrophages EDAT- 2021/05/04 06:00 MHDA- 2021/05/04 06:00 CRDT- 2021/05/03 06:37 PHST- 2021/02/27 00:00 [revised] PHST- 2019/10/09 00:00 [received] PHST- 2021/04/05 00:00 [accepted] PHST- 2021/05/03 06:37 [entrez] PHST- 2021/05/04 06:00 [pubmed] PHST- 2021/05/04 06:00 [medline] AID - 10.1002/jcb.29938 [doi] PST - aheadofprint SO - J Cell Biochem. 2021 May 3. doi: 10.1002/jcb.29938.