Carcinoma-associated perisinusoidal laminin may signal tumour cell metastasis to the liver

Abstract

The perisinusoidal space of the liver shows extensive modulation of the extracellular matrix in response to various pathological conditions. We studied perisinusoidal laminin expression immunohistochemically using polyclonal and monoclonal antibodies in 110 human liver specimens obtained at autopsy. In normal adult liver the perisinusoidal spaces contained only minimal amounts of immunoreactive laminin. In 86% of patients dying from cancer with liver metastasis, however, a distinct increase in the amount of perisinusoidal laminin could be demonstrated. The perisinusoidal space also contained laminin in cancer patients without liver metastasis. In 3 cases of leukaemia sinusoids were laminin negative. In cirrhosis and chronic passive congestion there was, as expected, laminin immunoreactivity in the perisinusoidal space. The results obtained using polyclonal antibodies against laminin were confirmed using chain-specific monoclonal antibodies against B2 laminin. In an ex vivo assay, viable tumour cells (Panc-1 and clone A) were found to bind with remarkable specificity to frozen sections of liver tissue containing perisinusoidal laminin as opposed to liver tissues without laminin. We suggest that this perisinusoidal laminin may directly on indirectly mediate tumour cell metastasis to the liver.