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


Authors: Mc Donnell, S.; Chaudhry, V.; Mansilla-Soto, J.; Zeng, Z. S.; Shu, W. P.; Guillem, J. G.
Article Title: Metastatic and non-metastatic colorectal cancer (CRC) cells induce host metalloproteinase production in vivo
Abstract: Numerous studies have demonstrated the persistent localization of matrix metalloproteinase (MMP) expression to the interface between invading human colorectal cancer (CRC) cells and surrounding stroma supporting a role for MMPs in CRC invasion and metastasis. The present study sought to determine whether CRC cells of varying metastatic potential would have differential effects on host MMP release. Subcutaneous CRC tumors were generated in BALB/c nude mice using three CRC cell lines: SW480, SW620, and the highly metastatic SW620S5 clone. Representative samples from the subcutaneous CRC were then orthotopically implanted on the cecum of recipient nude mice. Subcutaneous 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 nor MMP-9. In contradistinction, the subcutaneous tumors expressed limited amounts of MMP-2 and MMP-9 while the cecal tumors expressed significant amounts 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 determined by zymography and western blot analysis. In situ hybridization also localized the mRNA for MMP-9 to the host stromal cells. In conclusion, CRC cells 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 regulating factor(s) in vivo.
Keywords: controlled study; human cell; nonhuman; colorectal cancer; mouse; animals; mice; animal tissue; metastasis; gelatinase b; animal experiment; animal model; enzyme activation; tumor cells, cultured; mice, inbred balb c; colorectal neoplasms; in situ hybridization; enzyme regulation; mice, nude; reverse transcriptase polymerase chain reaction; cancer cell; neoplasm metastasis; base sequence; neoplasm transplantation; dna primers; stroma cell; enzyme release; cell invasion; enzyme localization; enzyme synthesis; metalloproteinase; gelatinase a; matrix metalloproteinase 9; matrix metalloproteinase 2; humans; human; male; article
Journal Title: Clinical and Experimental Metastasis
Volume: 17
Issue: 4
ISSN: 0262-0898
Publisher: Springer  
Date Published: 1999-06-01
Start Page: 341
End Page: 349
Language: English
PUBMED: 10545021
PROVIDER: scopus
DOI: 10.1023/A:1006651019335
DOI/URL:
Notes: Article -- Export Date: 16 August 2016 -- Source: Scopus
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  1. Jose Guillem
    414 Guillem
  2. Zhaoshi Zeng
    87 Zeng
  3. Weiping Shu
    18 Shu