CCL3-CCR5 axis promotes cell migration and invasion of colon adenocarcinoma via Akt signaling pathway

Background Infiltration of tumor-associated macrophages (TAMs) can promote tumorigenesis and development. C-C motif chemokine ligand 3 (CCL3) was reported to be derived from TAMs and tumor cells and facilitate the progression of several cancers. Nevertheless, whether CCL3 can be derived from TAMs and tumor cells of colon adenocarcinoma (COAD) is unclarified. Methods Peripheral blood monocytes-derived macrophages were polarized by the conditioned medium from COAD cells to establish TAM-like macrophages (TAM1/2). RT-qPCR and western blotting were used for detection of expression levels of CCL3 and its receptors C-C motif chemokine receptor 1 (CCR1) and CCR5 in TAM1/2 and COAD cells. Immunofluorescence staining was utilized for evaluating CCL3, CD163 and CCR5 expression. The Akt signaling pathway-associated protein levels were measured by western blotting. Transwell assays were used for assessing cell migration and invasiveness. Results CCL3 displayed a high level in TAMs and cancer cells of COAD. CCL3 activated the Akt signaling pathway by binding to CCR5. CCL3-CCR5 axis facilitated COAD cell migration and invasiveness by activating the Akt signaling. CCL3 derived from both TAMs and cancer cells contributed to the malignant behaviors of COAD cells. High expression of CCL3/CCR5 was closely associated with poor prognoses of COAD patients. Conclusion CCL3-CCR5 interaction promotes cell migration and invasiveness, and functions as a prognostic biomarker for COAD.

Automated summary

The study finds that CCL3 can be derived from TAMs and tumor cells of colon adenocarcinoma (COAD), and it promotes the migration and invasiveness of COAD cells by activating the Akt signaling pathway through binding to CCR5. High expression of CCL3/CCR5 is closely associated with poor prognosis of COAD patients.