IL-23 directly enhances the proliferative and invasive activities of colorectal carcinoma

Abstract

Abstract. plays an essential role in the mucosal immune system. It has been suggested that IL-23 is able to induce carcinogenesis as well as inflammation and a recent study revealed that IL-23R is expressed in colorectal carcinoma cells. However, neither the differences in the IL-23R expression among the patients nor the concrete functions of IL-23 in colorectal carcinoma cells have been revealed. The aim of the present study was to examine the characteristics of IL-23R expression in colorectal carcinoma and the direct effects of IL-23 on colorectal cancer cells. We examined the IL-23R expression in human colorectal cancer tissue samples by immunohistochemistry. Cell proliferation and invasion assays under IL-23 stimulation were performed using cultured cells derived from colorectal cancer. ELISA and real-time PCR were used to evaluate the transforming growth factor (TGF)-β production due to IL-23 stimulation. All of the TNM stage IV patients were positive for IL-23R. IL-23R expression in the carcinoma tissue was also relatively high at the deepest point of invasion in certain cases. The proliferative and invasive activities and/or TGF-β production of DLD-1 cells increased by IL-23 stimulation, whereas no change was observed in the activities of MIP101 and KM12c cells. IL-23 directly enhanced the malignancy of the colon carcinoma cells. An autocrine mechanism via TGF-β production may underlie these effects. IL-23 is therefore a potential target for cancer immunotherapy. However, the homogeneity in IL-23R expression and the effects of IL-23 on colorectal carcinoma cells should be considered.

Claudins and cancer: Fall of the soldiers entrusted to protect the gate and keep the barrier intact

“…Arguably, the deregulated barrier would facilitate the antigen-immune interaction to modulate local inflammatory response, which in turn can have important bearings upon tumorigenic processes. Notably, recent studies suggest that microbial infiltration through the deregulated barrier in transformed epithelium promotes colon cancer by activation of IL6-IL23 signaling [50,51]. In this regard, role of claudin proteins, especially claudin-1 and -2, in the regulation of mucosal inflammation has been demonstrated [46,52].…”

Self-renewal molecular mechanisms of colorectal cancer stem cells

“…STAT3 upregulates the expression of cell cycle regulators cyclin D1 , cyclin D2 , cyclin B , proto-oncogene myc , and anti-apoptotic genes Bcl-2 and Bcl-2-like 1 to promote proliferation and survival (130). IL-23 can promote CRC cells to generate TGF-β and induce the process of EMT to facilitate malignant transformation (131). Activated STAT5 by IL-23 with impaired Socs3 expression is associated with the metastasis of CRC (132), and the function of the IL-23/IL-17 axis on CRC initiation and progression has been recently recognized (133).…”

IL-23R is Epigenetically Regulated and Modulated by Chemotherapy in Non-Small Cell Lung Cancer

“…Expression of the IL-23R is associated with pro-inflammatory cues as it can be regulated by various cytokines including TNF-α (Charles et al, 2009), IL-6 (Zhou et al, 2007), IL-21, and IL-23 itself (Ivanov et al, 2007). Elevated levels of IL-23R receptor expression have also been demonstrated in ovarian cancer (Charles et al, 2009), NSCLC (Li et al, 2013) and in colorectal cancer (Lan et al, 2011; Suzuki et al, 2012). …”