Collagen type IV, laminin, alpha-smooth muscle actin (alphaSMA), alpha1 and alpha6 integrins expression in the liver with metastases from malignant gastrointestinal tumours.
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 alpha1 and alpha6 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 alpha-SMA, collagen type IV and alpha1 integrin chain, and appearance of laminin and alpha6 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 alpha-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 alpha1 and alpha6 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 alphaSMA, collagen type IV, laminin and of alpha1 and alpha6 integrin chains in sinusoids associated with metastases, might potentiate the further dissemination of tumour cells in new liver areas.
Gulubova
Maya Vladova
MV
Department of Pathology, Medical Faculty, Thracian University, Stara Zagora, Bulgaria. mgulubova@hotmail.com
D000199:Actins / Q000378:metabolism*; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D024141:Collagen Type IV / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D039423:Integrin alpha1 / Q000378:metabolism*; D039503:Integrin alpha6 / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology
D000199:Actins; D024141:Collagen Type IV; D039423:Integrin alpha1; D039503:Integrin alpha6; D007797:Laminin