Differential effects of anticoagulants on tumor development of mouse cancer cell lines B16, K1735 and CT26 in lung.
Cancer progression is facilitated by blood coagulation. Anticoagulants, such as Hirudin and low molecular weight heparins (LMWHs), reduce metastasis mainly by inhibition of thrombin formation and L- and P-selectin-mediated cell-cell adhesion. It is unknown whether the effects are dependent on cancer cell type. The effects of anticoagulants on tumor development of K1735 and B16 melanoma cells and CT26 colon cancer cells were investigated in mouse lung. Tumor load was determined noninvasively each week up to day 21 in all experiments using bioluminescence imaging. Effects of anticoagulants on tumor development of the three cell lines were correlated with the fibrin/fibrinogen content in the tumors, expression of tissue factor (TF), protease activated receptor (PAR)-1 and -4 and CD24, a ligand of L- and P-selectins. Hirudin inhibited tumor development of B16 cells in lungs completely but did not affect tumor growth of K1735 and CT26 cells. Low molecular weight heparin did not have an effect on K1735 melanoma tumor growth either. TF and PAR-4 expression was similar in the three cell lines. PAR-1 and CD24 were hardly expressed by K1735, whereas CT26 cells expressed low levels and B16 high levels of PAR-1 and CD24. Fibrin content of the tumors was not affected by LMWH. It is concluded that effects of anticoagulants are dependent on cancer cell type and are correlated with their CD24 and PAR-1 expression.
Niers
Tatjana M H
TM
Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Brüggemann
Lois W
LW
Klerk
Clara P W
CP
Muller
Femke J M
FJ
Buckle
Tessa
T
Reitsma
Pieter H
PH
Richel
Dick J
DJ
Spek
C Arnold
CA
Van Tellingen
Olaf
O
Van Noorden
Cornelis J F
CJ
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology* / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects; D051927:CD24 Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology / Q000627:therapeutic use; D006629:Hirudins / Q000494:pharmacology; D008175:Lung Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology* / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D019007:P-Selectin / Q000378:metabolism; D044463:Receptor, PAR-1 / Q000378:metabolism; D013925:Thromboplastin / Q000096:biosynthesis; D014183:Transplantation, Heterologous
D000925:Anticoagulants; D051927:CD24 Antigen; D006495:Heparin, Low-Molecular-Weight; D006629:Hirudins; D019007:P-Selectin; D044463:Receptor, PAR-1; D005337:Fibrin; D005340:Fibrinogen; D013925:Thromboplastin