A Chemerin Peptide Analog Stimulates Tumor Growth in Two Xenograft Mouse Models of Human Colorectal Carcinoma

Simple Summary The chemoattractant adipokine chemerin has been found to be elevated in several types of cancer, including colorectal carcinoma. The functional role of chemerin in colorectal carcinoma, however, has not been elucidated to date. This study analyses the impact of the chemerin analog CG34 on proliferation, colony formation, and migration in the human colorectal cancer cell lines HCT116, HT29 and SW620. In addition, the effect of systemic CG34 treatment is investigated in two xenograft mouse models of colorectal cancer (HCT116-luc and HT29-luc). The results of this study suggest there is a stimulatory role of chemerin receptor activation on the growth of colorectal carcinoma. Background: Chemerin plasma concentration has been reported to be positively correlated with the risk of colorectal cancer. However, the potential regulation of CRC tumorigenesis and progression has not yet been investigated in an experimental setting. This study addresses this hypothesis by investigating proliferation, colony formation, and migration of CRC cell lines in vitro as well as in animal models. Methods: In vitro, microscopic assays to study proliferation, as well as a scratch-wound assay for migration monitoring, were applied using the human CRC cell lines HCT116, HT29, and SW620 under the influence of the chemerin analog CG34. The animal study investigated HCT116-luc and HT29-luc subcutaneous tumor size and bioluminescence during treatment with CG34 versus control, followed by an ex-vivo analysis of vessel density and mitotic activity. Results: While the proliferation of the three CRC cell lines in monolayers was not clearly stimulated by CG34, the chemerin analog promoted colony formation in three-dimensional aggregates. An effect on cell migration was not observed. In the treatment study, CG34 significantly stimulated both growth and bioluminescence signals of HCT116-luc and HT29-luc xenografts. Conclusions: The results of this study represent the first indication of a tumor growth-stimulating effect of chemerin signaling in CRC.

Automated summary

This study reveals a stimulating effect of chemerin signaling on the growth of colorectal carcinoma. Both in vitro and in vivo experiments show that the chemerin analog CG34 promotes colony formation and tumor growth in colorectal cancer.