Coordinate cell-surface expression of matrix metalloproteinases and their inhibitors on cancer-associated myofibroblasts from malignant ascites in patients with gastric carcinoma.
OBJECTIVE
The crucial role of tumor stroma in cancer cell invasion has been described in human carcinoma tissues. However, myofibroblastic invasion remains largely unexplored in malignant ascites. Purpose of this study is to investigate the spatial localization or regulation of matrix metalloproteinases (MMP-2, -7 -9, MT1-MMP) and their inhibitors (TIMP-2 and -4) on myofibroblasts from malignant ascites in 20 patients with gastric carcinoma.


METHODS
The quantitative flow cytometric analysis of MMPs or TIMPs on myofibroblasts was based on the percentage of double positive cells defined by anti MMPs or anti TIMPs, and anti alpha-smooth muscle actin (alpha-SMA) antibodies.


RESULTS
The results clearly showed that the coordination of the high level of cell-surface expression of secreted MMPs and TIMPs was noted on the alpha-SMA+ myofibroblasts. The finding suggests the possible formation of ternary complex, MT1-MMP/TIMPs/MMPs on the cells. The events might be a cause and result of activation processing of MMPs on the cells.


CONCLUSIONS
This study provides the presence of invasive myofibroblasts with activated MMPs in close association with MMPs+ and TIMPs+ cancer cells and tumor-infiltrating lymphocytes from malignant ascites, emphasizing the importance of molecular cross-talk in tumor-host microenvironment for cancer invasion, metastasis and progression.
Koyama
Shohei
S
Department of Internal Medicine, Institute of Clinical Medicine, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba-City, Ibaraki, 305-8575, Japan. s-koyama@mail2.accsnet.ne.jp
D000368:Aged; D000970:Antineoplastic Agents / Q000378:metabolism; D001202:Ascitic Fluid / Q000166:cytology / Q000201:enzymology*; D002277:Carcinoma / Q000201:enzymology* / Q000556:secondary; D018450:Disease Progression; D005260:Female; D005347:Fibroblasts / Q000201:enzymology*; D005434:Flow Cytometry; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D008875:Middle Aged; D009379:Neoplasms, Muscle Tissue / Q000201:enzymology; D011480:Protease Inhibitors / Q000378:metabolism; D020239:Receptor Cross-Talk; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000473:pathology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*; D000097792:Tissue Inhibitor of Metalloproteinase-4
D000970:Antineoplastic Agents; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D019716:Tissue Inhibitor of Metalloproteinase-2; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4