Higher TNF-alpha production detected in colorectal cancer patients monocytes

Abstract

Many studies have shown that TNF-α is critically involved in tumor promotion and progression. We examined the ability of monocytes from patients with colorectal cancer in different stages of the disease to produce TNF-α after stimulation and the involvement of JNK signal transduction pathway in TNF-α synthesis. Purification of monocytes was done by plastic adherence of PBMC. Monocytes were stimulated with LPS or C3bgp. The involvement of JNK MAP kinase in TNF-α secretion was evaluated by using selective JNK inhibitor SP600125. The quantity determination of TNF-α was performed by ELISA in culture supernatants on 24 h. Monocytes from patients produced significantly higher level of TNF-α in response to LPS stimulation in comparison with monocytes isolated from healthy donors (1926±690 pg/ml vs. 1465±771 pg/ml; p=0.034). Moreover, we observed that LPS-stimulated TNF-α production increased in stage-dependent manner; because monocytes from patients with advanced cancer secreted significantly more TNF-α than monocytes from patients in early stage of the disease (2298±127 pg/ml vs. 1687±780 pg/ml; p=0.041). Inhibition of JNK MAPK led to significant suppression of TNF-α production in both healthy individuals and patients with colorectal cancer. However, even after inhibition of JNK, monocytes from patients produced a greater quantity TNF-α, compared with monocytes from healthy donors. We conclude that monocytes from patients with colorectal cancer are prone to produce higher levels of TNF-α after stimulation and this production is disease stage dependent.