Fig. 7

TAMs enhanced CRC tumorigenesis and metastasis in vivo. (a) The morphological characteristics of tumor xenograft, tumor size and tumor weight in the HCT116 alone, HCT116 + TAM/si-con and HCT116 + TAM/si-IL6 groups. Error bars, SD. (b) The relative expression of FoxQ1, CD163, IL6, E-cadherin and Vimentin mRNA of tumors from the HCT116 alone, HCT116 + TAM/si-con and HCT116 + TAM/si-IL6 groups; Error bars, SD. (c) IHC analyzed the expression of FoxQ1, CD163, IL6, E-cadherin and Vimentin protein of tumors from the HCT116 alone, HCT116 + TAM/si-con and HCT116 + TAM/si-IL6 groups; Scale bar, 200×. (d) IHC analyzed Ki67 expression in tumor from the HCT116 alone, HCT116 + TAM/si-con and HCT116 + TAM/si-IL6 groups; Scale bar, 200×. (e) Representative CTC images from two mice, respectively. Scale bar, 20 μm. (f) The ^MCTC ratio of mice blood from the HCT116 alone, HCT116 + TAM/si-con and HCT116 + TAM/si-IL6 groups. (g) Representative images of metastatic lesions in the liver from mice in the HCT116 + TAM/si-con groups at 30 days after implantation, and representative hematoxylin and eosin–stained sections of metastatic nodules in liver and lung are shown. Scale bar, 200×. (h) Percentage of mice with metastasis is indicated from HCT116 alone, HCT116 + TAM/si-con and HCT116 + TAM/si-IL6 groups (n = 6 per group). (i) Weight of nude mice was monitored every 5 days after being injected with HCT116 alone, HCT116 + TAM/si-con and HCT116 + TAM/si-IL6 via the tail veins; (j) Schematic illustration of the crosstalk between TAMs and cancer cells in the tumor microenvironment. Our study illustrated a crosstalk between TAMs and cancer cells in the CRC microenvironment. IL6, secreted by TAMs, binds to the IL6 receptor (IL6R) on the cancer cell surface to phosphorylate STAT3. pSTAT3 is translocated to the nucleus to regulate expression of a number of miRNAs, including miR-506-3p, which facilitates the EMT program to mediate ^MCTC generation, thereby enhancing the migration, invasion, and metastatic potential of CRC cells through miR-506-3p/FoxQ1 axis. In a positive feedback loop, FoxQ1 promoted the secretion of CCL2 from TAMs-educated CRC cells, which increase the recruitment of macrophages. Error bars, SD. *P < 0.05; **P < 0.01; ***P < 0.001