Our results provide novel evidence that hypomethylation of specific LINE-1 elements permits inadvertent activation of methylation-silenced MET, RAB3IP and CHRM3 proto-oncogenes in CRC metastasis.
Mice with subcutaneous transplants of ACCIM were subdivided into six groups and intraperitoneally received one of the following treatments daily for 5 weeks: a) PBS (control), b) AMD3100 (CXCR4 antagonist), c) L-NAME (NOS inhibitor), d) 1400W (iNOS inhibitor), e) both AMD3100 and L-NAME (AMD3100+L-NAME) and f) both AMD3100 and 1400W (AMD3100+1400W).
This treatment protocol produces a 4-fold reduction in the number of tumors, a 17-fold reduction in the relative tumor burden, and a 5-fold reduction in invasion and metastasis when compared with mice exposed to liposome-encapsulated PBS or PBS.