PMID- 30730243 OWN - NLM STAT- MEDLINE DCOM- 20200518 LR - 20200518 IS - 1557-7465 (Electronic) IS - 1079-9907 (Linking) VI - 39 IP - 4 DP - 2019 Apr TI - MCP-1/CCL2 Mediated by Autocrine Loop of PDGF-BB Promotes Invasion of Lung Cancer Cell by Recruitment of Macrophages Via CCL2-CCR2 Axis. PG - 224-232 LID - 10.1089/jir.2018.0113 [doi] AB - Platelet-derived growth factor-BB (PDGF-BB) is recognized as a potential player in a paracrine manner in tumor stroma development. PDGF-BB has an autocrine growth function in lung cancer cells; however, the mechanism in nonsmall-cell lung cancer is not fully understood. In this study, we report that PDGF-BB increased monocyte chemoattractant protein-1 (MCP-1)-dependent macrophage recruitment and that expression of metastatic genes increased in A549 cells cocultured with RAW 264.7 macrophages. Similar to exogenous PDGF-BB, PDGF-BB might have a self-stimulation in invasion of cancer cells during reciprocal activation of cancer cells and tumor-associated macrophages through secretion of soluble proteins. Also, we found that PDGF-BB upregulates both mRNA and protein level of MCP-1 expression in human A549 cells through mitogen-activated protein kinases and phosphatidylinositol 3-kinase/Akt cell signaling pathways, binding NFkappaB to MCP-1 promoter site and PDGF-Rbeta as critical receptor. These results suggested that MCP-1/chemokine (C-C motif) ligand 2 (CCL2) expression mediated by the autocrine loop of PDGF-BB enhanced recruitment of macrophages through CCL2-CCR2 axis, which could ultimately increase expression of metastatic genes in lung cancer cells, finally promoting invasive potential of cancer cells. FAU - Ding, Mei AU - Ding M AD - Department of Respiratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, P. R. China. FAU - He, Shao-Jun AU - He SJ AD - Department of Respiratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, P. R. China. FAU - Yang, Jiong AU - Yang J AD - Department of Respiratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, P. R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190207 PL - United States TA - J Interferon Cytokine Res JT - Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research JID - 9507088 RN - 0 (CCL2 protein, human) RN - 0 (CCR2 protein, human) RN - 0 (Ccl2 protein, mouse) RN - 0 (Ccr2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Receptors, CCR2) RN - 1B56C968OA (Becaplermin) SB - IM MH - Animals MH - *Autocrine Communication MH - Becaplermin/*metabolism MH - Cells, Cultured MH - Chemokine CCL2/*metabolism MH - Humans MH - Lung Neoplasms/*metabolism/pathology MH - Macrophages/*metabolism MH - Mice MH - RAW 264.7 Cells MH - Receptors, CCR2/*metabolism OTO - NOTNLM OT - MCP-1 (CCL2) OT - PDGF-BB OT - invasion OT - lung cancer OT - macrophages EDAT- 2019/02/08 06:00 MHDA- 2020/05/19 06:00 CRDT- 2019/02/08 06:00 PHST- 2019/02/08 06:00 [pubmed] PHST- 2020/05/19 06:00 [medline] PHST- 2019/02/08 06:00 [entrez] AID - 10.1089/jir.2018.0113 [doi] PST - ppublish SO - J Interferon Cytokine Res. 2019 Apr;39(4):224-232. doi: 10.1089/jir.2018.0113. Epub 2019 Feb 7.