The role of β-adrenergic receptors and CC chemokine receptor 6 in the progression of colorectal cancer

• Main Authors: Chih Chien Chin, 靳志堅
• Other Authors: C. S. Shi
• Format: Others
• Language: en_US
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/gqx2ng

博士 === 長庚大學 === 臨床醫學研究所 === 105 === Colorectal cancer (CRC) is the first prevalent cancer in Taiwan and also a leading cause of cancer-related deaths worldwide. Both epidemiological and animal studies have demonstrated the promotional effect of chronic stress associated secretion of catecholamines on the progression of various cancers including CRC, mainly through β-adrenergic receptors (β-ARs)- dependent mechanisms. CC chemokine receptor 6 (CCR6) and IL-17 have been found to be associated with CRC migration and prognosis. However, the evidence regarding the direct blockage of β1/2-AR signaling in CRC has not been thoroughly analyzed yet, and the relationship between IL-17 and CCR6 in CRC cell’s migration remains unclear. Our study uses in vitro and in vivo methods, and clinical CRC tissues to investigate the characteristics of β1/2-ARs signaling blockage and activity on CRC functions, and uses migration assay to explore the correlation between IL-17, CCR6, and CRC cell’s migration. We found that inhibition of β2-AR but not β1-AR signaling selectively suppressed cell viability of certain CRC cells, induced G1-phase cell cycle arrest, and caused apoptosis. We also confirmed that β2-AR blockage could inhibit the growth of CRC xenograft. Our results demonstrated that β2-AR antagonism selectively represses the growth of CRC cells that potentially carry wild-type KRAS via the inhibition of β2-AR transactivated EFGR- Akt/ERK1/2 signaling. Our study also revealed that IL-17 could induce the expressions of CCR6 and CCL20 and subsequent migration of CRC cells. Both of β2-AR and CCR6 might be the potential targets of further CRC therapy and worth to be worked on.