On the mechanism of sitagliptin inhibition of colorectal cancer cell lines ’ metastatic functionalities

SummaryThe cell membrane glycoprotein CD26 with peptidase activity (DPP4) and/or its soluble CD26/DPP4 counterpart expression and/or activity are altered in several cancers. Its role in metastasis development was recently highlighted by the discovery of CD26+ CSCs subsets and the fact that clinical DPP4 inhibitors showed anti ‐metastatic effects in animal models. Also, diabetic patients treated with the DPP4 inhibitor sitagliptin showed greater overall survival after colorectal or lung cancer surgery than patients under other diabetic therapies.However, the mechanism of action of these inhibitors in this context is unclear. We studied herein the role of CD26 and its DPP4 enzymatic activity in malignant cell features such as cell ‐to‐cell homotypic aggregation, cancer cell motility and invasion in a panel of human colorectal cancer (CRC) cell lines, avoiding models that include the physiological role of DPP4 in chemotaxis.Present results indicate that CD26 participates in the induction of cell invasion, motility, and aggregation of CD26 ‐positive CRC cell lines. Moreover, only invasion and motility assays, which are collagen matrix‐dependent, showed a decrease upon treatment with the DPP4 inhibitor sitagliptin. Sitagliptin showed opposite effects to that of TGF‐β1 on EMT and cell cycle, but this result does not explain its C D26/DPP4‐dependent effect.These results contribute to the elucidation of the molecular mechanisms behind sitagliptin inhibition of metastat...
Source: IUBMB Life - Category: Research Authors: Tags: RESEARCH COMMUNICATION Source Type: research