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Role of sinusoidal heparan sulfate proteoglycan in liver metastasis formation

✍ Scribed by József Tóvári; Sándor Paku; Erzsébet Rásó; Gábor Pogány; Ilona Kovalszky; Andrea Ladányi; Károly Lapis; József Tímár


Publisher
John Wiley and Sons
Year
1997
Tongue
French
Weight
280 KB
Volume
71
Category
Article
ISSN
0020-7136

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✦ Synopsis


Previous studies have indicated that the predominant sites of tumor cell extravasation in the liver are the sinusoidal vessels, where tumor cells contact the sinusoidal endothelium and the subendothelial extracellular matrix containing the basic components of the basement membrane. We studied the role of sinusoidal extracellular matrix in metastatsis formation by 3LL-HH murine tumor cells selected for their preferential liver colonization. 3LL-HH tumor cells did not efficiently adhere to cryosections of the liver, but they recognized the sinusoids and vessel walls. Pre-treatment of the mice with polyclonal anti-basement membrane antibodies [anti-laminin, anti-fibronectin and anti-heparan sulfate proteoglycan (HSPG)] significantly modulated the organ distribution of tumor cell colonies following intracardial injection: all 3 antibodies inhibited kidney colonization; antilaminin and anti-fibronectin antibodies inhibited lung colonization; and only anti-HSPG antibody inhibited liver colonization. In several organs such as the heart, stomach, pancreas and bladder, anti-basement membrane antibody treatment did not alter the process of colonization. Immunofluorescence studies showed that anti-HSPG antibody recognized the basement membranes of sinusoids and blood vessels. Our data suggest a specific involvement of sinusoidal HSPG in the liver colonization of 3LL-HH cells.


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