Abstract
Tumor invasion and metastasis are complex processes, requiring the ability of tumor cells to interact with proteins of the extracellular matrix through cell-adhesion molecules on the cell surface. Integrins are heterodimeric membrane glycoproteins, consisting of α and β subunits, which enable cells to recognize adhesive substrates in the extracellular matrix. The roles of the integrinα 5 β 1 in tumor invasion are highlighted by finding that some tumor cells have lost or reducedα 5 β 1 expression. It therefore functions as a negative signaling regulator. Expression ofα 5 β 1 and its mediation of cell adhesion in hepatocellular carcinoma (HCC) have not been elucidated. In surgical specimens of HCC we found, by immunohistochemistry and Northern blot analysis, that theα 5-positive rates in cancerous tissues were lower than the corresponding rates in non-cancerous tissues. Reduced expression of the integrinα 5 occurred more frequently in HCC with more malignant phenotypes, such as poor differentiation, large size (more than 10-cm in diameter), absence of capsule and high invasion. Reverse transcription/polymerase chain reaction, a more sensitive assay, was used to detect theα 5 mRNA level in LCID20, a highly metastatic model of human HCC, and LCID35, a low-metastasis model. The results showed that integrinα 5 was negative in the former and positive in the latter. Cell adhesion assays showed the maximal percentage inhibition of anti-α 5 mAb on SMMC 7721 cell adhesion to fibronectin to be 68.9±4.9% at the saturation concentrations of each antibody (200 μg/ml). If anti-α 5 mAb was combined with anti-β 1 mAb, the inhibition was 74.1±11.1%. It is concluded that reduced expression of the integrinα 5 subunit is correlated with more malignant phenotypes of human HCC. Any change in the adhesion of hepatocellular carcinoma cells to fibronectin is mainly dependent upon the function of the integrinα 5 β 1.
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This work is supported by a Grant of Leading Speciality by Shanghai Health Bureau, Shanghai Education Bureau and American Chinese Medical Board (no. 93583)
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Yao, M., Zhou, XD., Zha, XL. et al. Expression of the integrinα 5 subunit and its mediated cell adhesion in hepatocellular carcinoma. J Cancer Res Clin Oncol 123, 435–440 (1997). https://doi.org/10.1007/BF01372547
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DOI: https://doi.org/10.1007/BF01372547