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Collagen type IV, laminin, α-smooth muscle actin (αSMA), α1 and α6 integrins expression in the liver with metastases from malignant gastrointestinal tumours

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Abstract

Basement membrane proteins and integrins can profoundly affect the biological behaviour of metastasic tumour cells. Using light and ultrastructural immunohistochemistry, we showed the presence of alterations in the occurrence of collagen type IV and laminin, and the expression of α1 and α6 integrin chains in the livers of patients with metastases from gastric, colorectal and pancreatic cancers. The myofibroblast-like cells in the metastatic stroma were studied. Parallel expressions of α-SMA, collagen type IV and α1 integrin chain, and appearance of laminin and α6 integrin chain immunoreactivity in the extratumoral liver tissue were markedly increased in sinusoids associated with metastases. Furthermore, ultrastructural immunohistochemistry detected tumour cells adhered to amorphous laminin deposits in the metastases. Laminin occurrence in liver sinusoids was visible as fine amorphous deposits in the space of Disse. The similarity between α-SMA-positive stromal cells in metastatic stroma and hepatic stellate cells (HSCs) was established by the presence of lipid droplets in their cytoplasm. The immune deposits of α1 and α6 integrin chains were observed on the hepatocyte microvilli and on the membrane of sinusoidal endothelial cells. These findings suggest that metastatic cells produce stimuli that induce HSCs activation and sinusoidal changes. In addition, the enhanced parallel expression of αSMA, collagen type IV, laminin and of α1 and α6 integrin chains in sinusoids associated with metastases, might potentiate the further dissemination of tumour cells in new liver areas.

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Gulubova, M.V. Collagen type IV, laminin, α-smooth muscle actin (αSMA), α1 and α6 integrins expression in the liver with metastases from malignant gastrointestinal tumours. Clin Exp Metastasis 21, 485–494 (2004). https://doi.org/10.1007/s10585-004-3171-x

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