Inhibition of pulmonary metastasis in a human MT3 breast cancer xenograft model by dual liposomes preventing intravasal fibrin clot formation.
The process of metastasis formation in cancer is not completely understood and is the main reason cancer therapies fail. Previously, we showed that dual liposomes simultaneously containing the hemostatic inhibitor, dipyridamole and the anticancer drug, perifosine potently inhibited metastasis, causing a 90% reduction in the number of lung metastases in a murine experimental metastasis model. To gain deeper insight into the mechanisms leading to the inhibition of metastasis by these dual liposomes, in the present study, the development of metastases by MT3 breast cancer cells in a mouse xenograft model was analyzed in more detail with regard to tumor cell settlement and metastatic growth. We found that the development of lung metastases by MT3 tumor cells is essentially dependent on the formation of fibrin clots as a precondition for the pulmonary arrest of tumor cells and the subsequent intravascular expansion of micrometastases before their invasion into the surrounding tissue.
Wenzel
Jane
J
Max-Delbrück-Center for Molecular Medicine Berlin-Buch, Berlin, Germany. j.wenzel@mdc-berlin.de
Zeisig
Reiner
R
Haider
Wolfram
W
Habedank
Sylvia
S
Fichtner
Iduna
I
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001777:Blood Coagulation / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects; D045744:Cell Line, Tumor; D004176:Dipyridamole / Q000008:administration & dosage; D005260:Female; D005337:Fibrin; D006801:Humans; D008081:Liposomes; D008168:Lung / Q000098:blood supply; D008175:Lung Neoplasms / Q000556:secondary*; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D000090023:Metallothionein 3; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000031:analogs & derivatives; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D008081:Liposomes; D000090023:Metallothionein 3; C000715430:Mt3 protein, mouse; D010975:Platelet Aggregation Inhibitors; D010767:Phosphorylcholine; C105905:perifosine; D004176:Dipyridamole; D005337:Fibrin