title: Coagulation facilitates tumor cell spreading in the pulmonary vasculature during early metastatic colony formation.
abstract: Coagulation has long been known to facilitate metastasis. To pinpoint the steps where coagulation might play a role in the metastasis, we used three-dimensional visualization of direct infusion of fluorescence labeled antibody to observe the interaction of tumor cells with platelets and fibrinogen in isolated lung preparations. Tumor cells arrested in the pulmonary vasculature were associated with a clot composed of both platelets and fibrin(ogen). Initially, the cells attached to the pulmonary vessels were rounded. Over the next 2 to 6 hours, they spread on the vessel surface. The associated clot was lysed coincident with tumor cell spreading. To assess the importance of clot formation, we inhibited coagulation with hirudin, a potent inhibitor of thrombin. The number of tumor cells initially arrested in the lung of hirudin-treated mice was essentially the same as in control mice. However, tumor cell spreading and subsequent retention of the tumor cells in the lung was markedly inhibited in the anticoagulated mice. These associations of the tumor cells with platelets were independent of tumor cell expression of P-selectin ligands. This work identifies tumor cell spreading onto the vascular surface as an important component of the metastatic cascade and implicates coagulation in this process.
authors.affiliation: Department of Pathology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Jae Hong
authors.initials: JH
authors.lastname: Im
authors.forename: Weili
authors.initials: W
authors.lastname: Fu
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Sujata K
authors.initials: SK
authors.lastname: Bhatia
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Hammer
authors.forename: M Anna
authors.initials: MA
authors.lastname: Kowalska
authors.forename: Ruth J
authors.initials: RJ
authors.lastname: Muschel
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000556:secondary; D000818:Animals; D001777:Blood Coagulation; D001792:Blood Platelets / Q000473:pathology; D002450:Cell Communication / Q000502:physiology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000097:blood / Q000473:pathology; D005340:Fibrinogen / Q000378:metabolism; D005354:Fibrosarcoma / Q000097:blood / Q000556:secondary; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D008168:Lung / Q000098:blood supply* / Q000473:pathology; D008175:Lung Neoplasms / Q000097:blood* / Q000556:secondary*; D008545:Melanoma / Q000097:blood / Q000556:secondary; D008546:Melanoma, Experimental / Q000097:blood / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000097:blood* / Q000473:pathology*; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D051381:Rats; D013917:Thrombin / Q000037:antagonists & inhibitors
chemical_list: D006629:Hirudins; D005340:Fibrinogen; D013917:Thrombin