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Invasiveness of hepatocellular carcinoma cell lines: contribution of membrane-type 1 matrix metalloproteinase.

ABSTRACT: Intrahepatic metastasis is one of the malignant features of hepatocellular carcinoma (HCC). Matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (u-PA)/plasmin, are known to be associated with the invasive properties of various types of tumor cells. In this study, we examined which proteinases play a role in the metastatic invasion of human HCC cell lines. JHH-5 and JHH-6 cells constitutively expressed mRNAs for both membrane-type 1 matrix metalloproteinase (MT1-MMP) and u-PA and invaded through reconstituted MATRIGEL in vitro, whereas JHH-7 cells expressed u-PA mRNA but not MT1-MMP and did not invade. However, hepatocyte growth factor (HGF) induced MT1-MMP expression on the surface of JHH-7 cells and markedly increased invasiveness of JHH-7 in a concentration-dependent manner. Moreover, cleavage activity for pro-MMP-2 was induced in HGF-treated JHH-7 cells. MMP inhibitor, rather than serine proteinase inhibitor, potently inhibited HCC cell invasion. Intrahepatic injection of HCC cell lines into athymic nude mice caused visible intrahepatic metastases in vivo. Moreover, JHH-7 tumors showed expression of MT1-MMP mRNA, while in vitro cultured JHH-7 cells did not. These findings suggest that MT1-MMP plays an important role in the invasive properties of HCC cells, and that HGF modifies the invasive properties of noninvasive HCC cells.

SUBMITTER: Murakami K

PROVIDER: S-EPMC1508115 | biostudies-literature | 1999 Nov

REPOSITORIES: biostudies-literature

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Invasiveness of hepatocellular carcinoma cell lines: contribution of membrane-type 1 matrix metalloproteinase.

Murakami K K Sakukawa R R Ikeda T T Matsuura T T Hasumura S S Nagamori S S Yamada Y Y Saiki I I

Neoplasia (New York, N.Y.) 19991101 5

Intrahepatic metastasis is one of the malignant features of hepatocellular carcinoma (HCC). Matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (u-PA)/plasmin, are known to be associated with the invasive properties of various types of tumor cells. In this study, we examined which proteinases play a role in the metastatic invasion of human HCC cell lines. JHH-5 and JHH-6 cells constitutively expressed mRNAs for both membrane-type 1 matrix metalloproteinase (MT1-MMP) and u-P ...[more]

PMID: 10933057

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Project description:Background:Biomarkers like programmed death ligand-1 (PDL1) have become a focal point for immunotherapeutic checkpoint inhibition in head and neck squamous cell carcinoma (HNSCC). However, it's only part of the total immunosuppressive biomarker profile of HNSCC cells. Matrix metalloproteinases (MMPs) are enzymes that break down the basement membrane allowing cancer cells to metastasize and play an important role in the tumor microenvironment. MMPs can also activate certain cytokines, growth factors, and chemokines post-translationally. The objective of this study was to determine MMP and biomarker profiles of seven different HNSCC cell lines. Methods:Authenticated cell lines were grown in minimal media at 1×106 viable cells/mL and incubated at 37 °C. After 24 hrs supernatants were collected, and adhering cells were lysed. Multiplex immunoassays were used to determine MMP1, MMP7, MMP9, IL-6, VEGFA, IL-1?, TNF-?, GM-CSF, IL-1RA, and IL-8 concentrations in supernatants. ELISAs were used to determine PDL1, CD47, FASL, and IDO concentrations in cell lysates. A one-way ANOVA was fit to examine log-transformed concentrations of biomarkers between seven HNSCC cell lines, and pairwise group comparisons were conducted using post- hoc Tukey's honest significance test (?=0.05). Results:Significant differences (P<0.05) in MMP and biomarker concentrations were found between the seven HNSCC cell lines. For example, MMP9 was highest in SCC25 and UM-SCC99, MMP7 was highest in SCC25 and UM-SCC19, and MMP1 was highest in SCC25. Conclusions:These results suggest different patients' HNSCC cells can express distinct profiles of select biomarkers and MMPs, which could be due to metastatic stage of the cancer, primary tumor site, type of tissue the tumor originated from, or genomic differences between patients. MMP and biomarker expression profiles should be considered when choosing cell lines for future studies. The results support the reason for personalized medicine and the need to further investigate how it can be used to treat HNSCC.

Dataset Information

Invasiveness of hepatocellular carcinoma cell lines: contribution of membrane-type 1 matrix metalloproteinase.

Publications

Invasiveness of hepatocellular carcinoma cell lines: contribution of membrane-type 1 matrix metalloproteinase.

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