Abstract
BackgroundThe upregulation of ADAM17 has been reported to be associated with invasion and metastasis in various tumors, however the molecular mechanism of ADAM17 in the progression of hepatocellular carcinoma (HCC) remain to be clarified. Human matrix metalloproteinase 21 (MMP21), the newest member of the MMP gene family, has been suggested to play an important role in embryogenesis and tumor progression. So far, nothing is known about the relationship between ADAM17 and MMP21.MethodsIn this study, the expression level of ADAM17 and MMP21 in HCC tissues was measured by immunohistochemistry. The Scratch wounding assay and Transwell were used to identify the invasion and metastasis ability. ELISA was used to evaluate the production of MMP21. Coimmunoprecipitation experiments demonstrated a direct association between ADAM17 and MMP21. HPLC was used to confirmed that ADAM17 participated in the maturation of MMP21.ResultsOur present data indicated that ADAM17 and MMP21 was significantly upregulated in human HCC tissues. Knockdown of ADAM17 in HCC inhibited cell invasion and metastasis. Moreover, ADAM17 regulates the secretion and expression of MMP21. Furthermore we discovered a direct association between ADAM17 and MMP21, and we also found MMP21 prodomain could be cleaved by ADAM17.ConclusionOur data suggest that ADAM17 plays an important role in the development of HCC invasion and metastasis and this function may be implement by MMP21.
Highlights
The upregulation of ADAM17 has been reported to be associated with invasion and metastasis in various tumors, the molecular mechanism of ADAM17 in the progression of hepatocellular carcinoma (HCC) remain to be clarified
ADAM17 and matrix metalloproteinase 21 (MMP21) are significantly upregulated in human HCC tissues, and there is a positive correlation between the two genes To examined the expression of ADAM17 and MMP21 in patients with HCC
We analyzed the expression of MMP21, and the result was consistent with ADAM17 (Fig. 1b)
Summary
The upregulation of ADAM17 has been reported to be associated with invasion and metastasis in various tumors, the molecular mechanism of ADAM17 in the progression of hepatocellular carcinoma (HCC) remain to be clarified. Human matrix metalloproteinase 21 (MMP21), the newest member of the MMP gene family, has been suggested to play an important role in embryogenesis and tumor progression. Hepatocellular carcinoma (HCC) is a highly aggressive and heterogeneous disease. The latest national cancer statistics released by the National Cancer (China) showed that the morbidity of hepatocellular carcinoma is 36.5 per. Because the enzyme is responsible for releasing soluble tumor necrosis factor-alpha (TNFα) from the plasmalemma, it is known as TNFα converting enzyme (TACE/ADAM17) [3]. ADAM17 protein was highly expressed in esophageal squamous cell carcinoma
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