Colorectal cancer is the source of one of the most common cancer-related deaths\nworldwide, where the main cause of patient mortality remains metastasis. The aim of this study\nwas to determine the role of CCL7 (chemokine (C-C motif) ligand 7) in tumor progression and\nfinding whether it could predict survival of colorectal cancer patients. Initially, our study focused\non the crosstalk between mesenchymal stem cells (MSCs) and CT26 colon carcinoma cells and\nresulted in identifying CCL7 as a chemokine upregulated in CT26 colon cancer cells cocultured with\nMSCs, compared with CT26 in monoculture in vitro. Moreover, we showed that MSCs enhance CT26\ntumor cell proliferation and migration. We analyzed the effect of CCL7 overexpression on tumor\nprogression in a murine CT26 model, where cells overexpressing CCL7 accelerated the early phase\nof tumor growth and caused higher lung metastasis rates compared with control mice. Microarray\nanalysis revealed that tumors overexpressing CCL7 had lower expression of immunoglobulins\nproduced by B lymphocytes. Additionally, using Jh mutant mice, we confirmed that in the CT26\nmodel, CCL7 has an immunoglobulin-, and thereby, B-cell-dependent effect on metastasis\nformation. Finally, higher expression of CCL7 receptor CCR2 (C-C chemokine receptor type 2) was\nassociated with shorter overall survival of colorectal cancer patients. Altogether, we showed that\nCCL7 is essentially involved in the progression of colorectal cancer in a CT26 mouse model and that\nthe expression of its receptor CCR2 could be related to a different outcome pattern of patients with\ncolorectal carcinoma.
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