Role of sinusoidal heparan sulfate proteoglycan in liver metastasis formation.
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; anti-laminin 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.
Tóvári
J
J
1st Institute of Pathology and Experimental Cancer Research, Semmelweis University of Medicine, Budapest, Hungary.
Paku
S
S
Rásó
E
E
Pogány
G
G
Kovalszky
I
I
Ladányi
A
A
Lapis
K
K
Tímár
J
J
D000818:Animals; D001485:Basement Membrane / Q000276:immunology / Q000502:physiology; D002455:Cell Division; D004730:Endothelium, Vascular / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000276:immunology; D005455:Fluorescent Antibody Technique; D019812:Heparan Sulfate Proteoglycans; D006493:Heparin / Q000031:analogs & derivatives* / Q000502:physiology; D006497:Heparan Sulfate / Q000276:immunology; D007116:Immunization, Passive; D007797:Laminin / Q000276:immunology; D008113:Liver Neoplasms / Q000098:blood supply / Q000556:secondary* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D011509:Proteoglycans / Q000276:immunology / Q000502:physiology*; D014407:Tumor Cells, Cultured
D005353:Fibronectins; D019812:Heparan Sulfate Proteoglycans; D006493:Heparin; D006497:Heparan Sulfate; D007797:Laminin; D011509:Proteoglycans; C036090:heparin proteoglycan; C071927:perlecan