Metastatic and non-metastatic colorectal cancer (CRC) cells induce host metalloproteinase production in vivo

Numerous studies have demonstrated the persistent localization of matrix me talloproteinase (MMP) expression to the interface between invading human co lorectal cancer (CRC) cells and surrounding stroma supporting a role for MM Ps in CRC invasion and metastasis. The present study sought to determine wh ether CRC cells of varying metastatic potential would have differential eff ects on host MMP release. Subcutaneous CRC tumors were generated in BALB/c nude mice using three CRC cell lines: SW480, SW620, and the highly metastat ic SW620S5 clone. Representative samples from the subcutaneous CRC were the n orthotopically implanted on the cecum of recipient nude mice. Subcutaneou s and cecal tumors were analyzed for MMP expression via zymography, western blot, and RT-PCR. In vitro, none of the three cell lines expressed MMP-2 n or MMP-9. In contradistinction, the subcutaneous tumors expressed limited a mounts of MMP-2 and MMP-9 while the cecal tumors expressed significant amou nts of MMP-2 and MMP-9 as well as other smaller members of the MMP family. MMP-9 mRNA and protein was confirmed as host in origin by RT-PCR with mouse specific primers and a mouse MMP-9 molecular weight of 105 kDa as determin ed by zymography and western blot analysis. In situ hybridization also loca lized the mRNA for MMP-9 to the host stromal cells. In conclusion, CRC cell s appear incapable of producing MMP-2 and MMP-9 in vitro but are capable of up-regulating host MMP production in vivo. Enhanced host MMP-9 production in metastatic CRC cell-derived subcutaneous and cecal tumors suggests that metastatic colon cells may acquire the expression of important MMP regulati ng factor(s) in vivo.