Disparate roles of CXCR3A and CXCR3B in regulating progressive properties of colorectal cancer cells

作者:Li, Hai*; Rong, Shikuo; Chen, Chao; Fan, Yayun; Chen, Tuo; Wang, Yong; Chen, Dongmei; Yang, Chun; Yang, Jiali*
来源:Molecular Carcinogenesis, 2019, 58(2): 171-184.
DOI:10.1002/mc.22917

摘要

Human C-X-C Motif Chemokine Receptor 3A (CXCR3A) and CXCR3B are two splice variants of CXCR3 that is involved in a variety of progressive processes of cancer cells, including proliferation, migration, invasion, and tumorigenicity. However, the molecular mechanisms of CXCR3 in colorectal cancer (CRC) remain incomplete understood. In the present study, a significantly up-regulated CXCR3 protein was firstly observed in CRC tissues and cell lines in comparison with the paired non-tumor tissues and normal intestinal epithelial cells, which was positively associated with CRC TNM stages. In contrast, CXCR3B was down-regulated in CRC tumor tissues compared with that in the corresponding paired paracancerous tissues, and negatively correlated with the TNM stages of cancer. Of interest, the overexpression of CXCR3A enhanced the progressive capacity of cell proliferation, migration, invasion in CRC LOVO and HCT116 cells in vitro, and the tumorigenicity in nude mice in vivo. Conversely, the overexpression of CXCR3B exhibited an opposite phenotype of CXCR3A, with an ability to inhibit the progressive properties in CRC cell lines in vitro and tumorigenesis in vivo. In addition, immunoblotting analysis further demonstrated that an increased expression of CXCR3A inhibited the expression of CXCR3B in CRC cells and NCM460 normal colon epithelial cells; vice verse, an overexpression of CXCR3B suppressed the expression of CXCR3A in these cells. These data imply that an interaction between the CXCR3A and CXCR3B may play an important regulatory role in tumorigenicity of CRC, which warrants for further investigation.