This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Im, J. H. Articles by Muschel, R. J. Search for Related Content PubMed PubMed Citation Articles by Im, J. H. Articles by Muschel, R. J.

Coagulation Facilitates Tumor Cell Spreading in the Pulmonary Vasculature during Early Metastatic Colony Formation

Departments of ¹ Pathology and ² Hematology, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; and ³ Department of Bioengineering and Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania

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.

This article has been cited by other articles:

				C. S. Alves, M. M. Burdick, S. N. Thomas, P. Pawar, and K. Konstantopoulos The dual role of CD44 as a functional P-selectin ligand and fibrin receptor in colon carcinoma cell adhesion Am J Physiol Cell Physiol, April 1, 2008; 294(4): C907 - C916. [Abstract] [Full Text] [PDF]

				H. H. Versteeg, F. Schaffner, M. Kerver, H. H. Petersen, J. Ahamed, B. Felding-Habermann, Y. Takada, B. M. Mueller, and W. Ruf Inhibition of tissue factor signaling suppresses tumor growth Blood, January 1, 2008; 111(1): 190 - 199. [Abstract] [Full Text] [PDF]

				N. Hostettler, A. Naggi, G. Torri, R. Ishai-Michaeli, B. Casu, I. Vlodavsky, and L. Borsig P-selectin- and heparanase-dependent antimetastatic activity of non-anticoagulant heparins FASEB J, November 1, 2007; 21(13): 3562 - 3572. [Abstract] [Full Text] [PDF]

				S. Jain, M. Zuka, J. Liu, S. Russell, J. Dent, J. A. Guerrero, J. Forsyth, B. Maruszak, T. K. Gartner, B. Felding-Habermann, et al. Platelet glycoprotein Ib{alpha} supports experimental lung metastasis PNAS, May 22, 2007; 104(21): 9024 - 9028. [Abstract] [Full Text] [PDF]

				Y. Matsuo, S. Amano, M. Furuya, K. Namiki, K. Sakurai, M. Nishiyama, T. Sudo, K. Tatsumi, T. Kuriyama, S. Kimura, et al. Involvement of p38{alpha} Mitogen-activated Protein Kinase in Lung Metastasis of Tumor Cells J. Biol. Chem., December 1, 2006; 281(48): 36767 - 36775. [Abstract] [Full Text] [PDF]

				T. Goerge, A. Barg, E.-M. Schnaeker, B. Poppelmann, V. Shpacovitch, A. Rattenholl, C. Maaser, T. A. Luger, M. Steinhoff, and S. W. Schneider Tumor-derived matrix metalloproteinase-1 targets endothelial proteinase-activated receptor 1 promoting endothelial cell activation. Cancer Res., August 1, 2006; 66(15): 7766 - 7774. [Abstract] [Full Text] [PDF]

				C. Medina, P. Jurasz, M. J. Santos-Martinez, S. S. Jeong, T. Mitsky, R. Chen, and M. W. Radomski Platelet Aggregation-Induced by Caco-2 Cells: Regulation by Matrix Metalloproteinase-2 and Adenosine Diphosphate J. Pharmacol. Exp. Ther., May 1, 2006; 317(2): 739 - 745. [Abstract] [Full Text] [PDF]

				W. J. Lubbe, Z. Y. Zhou, W. Fu, D. Zuzga, S. Schulz, R. Fridman, R. J. Muschel, S. A. Waldman, and G. M. Pitari Tumor epithelial cell matrix metalloproteinase 9 is a target for antimetastatic therapy in colorectal cancer. Clin. Cancer Res., March 15, 2006; 12(6): 1876 - 1882. [Abstract] [Full Text] [PDF]

				H. Laubli, J. L. Stevenson, A. Varki, N. M. Varki, and L. Borsig L-Selectin Facilitation of Metastasis Involves Temporal Induction of Fut7-Dependent Ligands at Sites of Tumor Cell Arrest Cancer Res., February 1, 2006; 66(3): 1536 - 1542. [Abstract] [Full Text] [PDF]

				J. L. Stevenson, S. H. Choi, and A. Varki Differential Metastasis Inhibition by Clinically Relevant Levels of Heparins--Correlation with Selectin Inhibition, Not Antithrombotic Activity Clin. Cancer Res., October 1, 2005; 11(19): 7003 - 7011. [Abstract] [Full Text] [PDF]

				M. Belting, J. Ahamed, and W. Ruf Signaling of the Tissue Factor Coagulation Pathway in Angiogenesis and Cancer Arterioscler. Thromb. Vasc. Biol., August 1, 2005; 25(8): 1545 - 1550. [Abstract] [Full Text] [PDF]

				W. S. El-Deiry Meeting Report: The International Conference on Tumor Progression and Therapeutic Resistance Cancer Res., June 1, 2005; 65(11): 4475 - 4484. [Abstract] [Full Text] [PDF]

				T. A. Guise Thromboembolism to Metastasis: The Platelet-Lysophosphatidic Acid Connection IBMS BoneKEy, March 1, 2005; 2(3): 12 - 16. [Full Text] [PDF]