Tumor-associated macrophages favor C26 murine colon carcinoma cell proliferation in an oxidative stress-dependent manner

• Published in: Oncology reports Vol. 37; no. 4; pp. 2472 - 2480
• Main Authors: Luput, Lavinia, Licarete, Emilia, Sesarman, Alina, Patras, Laura, Alupei, Marius Costel, Banciu, Manuela
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.04.2017; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: Angiogenesis; Animals; Care and treatment; Cell growth; Cell Line, Tumor; Cell Proliferation; Coculture Techniques; Colon cancer; colon carcinoma; Colonic Neoplasms - blood supply; Colonic Neoplasms - immunology; Colonic Neoplasms - pathology; Colorectal cancer; Cytokines; Cytokines - metabolism; Deoxyribonucleic acid; Development and progression; DNA; Education; Fibroblasts; Granulocytes; Health aspects; Humans; Inflammation; Insulin-like growth factors; Ligands; Macrophages; Macrophages - cytology; Macrophages - immunology; Mice; NADPH oxidase; NADPH Oxidases - metabolism; Oxidative Stress; Physiology; proliferation; Proteins; Reactive Oxygen Species - metabolism; Transcription factors; Tumor Microenvironment; Tumor necrosis factor-TNF; tumor-associated macrophages; Vascular endothelial growth factor; Germany
• ISSN: 1021-335X; 1791-2431
• DOI: 10.3892/or.2017.5466

The role of tumor-associated macrophages (TAMs) in the development of colon carcinoma is still controversial. Therefore, the present study aimed to investigate the TAM-driven processes that may affect colon cancer cell proliferation. To achieve this purpose, murine macrophages were co-cultured with C26 murine colon carcinoma cells at a cell density ratio that approximates physiological conditions for colon carcinoma development in vivo. In this respect, the effects of TAM-mediated angiogenesis, inflammation and oxidative stress on the proliferative capacity of C26 murine colon carcinoma cells were studied. To gain insight into the TAM-driven oxidative stress, NADPH oxidase, the main pro-oxidant enzyme in macrophages, was inhibited. Our data revealed that the stimulatory effects of TAMs on C26 cell proliferation may be related mainly to their pro-oxidant actions exerted by NADPH oxidase activity, which maintains the redox status and the angiogenic capacity of the tumor microenvironment. Additionally, the anti-inflammatory and pro-angiogenic effects of TAMs on tumor cells were found to create a favorable microenvironment for C26 colon carcinoma development and progression. In conclusion, our data confirmed the protumor role of TAMs in the development of colon carcinoma in an oxidative stress-dependent manner that potentiates the angiogenic capacity of the tumor microenvironment. These data may offer valuable information for future tumor-targeted therapies based on TAM 're-education' strategies.