title: Increased efficacy of breast cancer chemotherapy in thrombocytopenic mice.
abstract: Platelets contribute to homeostasis of the tumor vasculature by helping prevent hemorrhage. Thus, we hypothesized that inducing thrombocytopenia would increase tumor vascular leakiness and facilitate the effective delivery of chemotherapeutic agents to tumors. In a mammary carcinoma murine model, platelet depletion induced bleeding specifically at the tumor site, favoring the accumulation of fluorescently labeled microspheres only in the tumor. Moreover, induction of thrombocytopenia in tumor-bearing mice before injection of paclitaxel increased its intratumoral accumulation and reduced growth of both slow- and fast-growing tumors, compared with mice with normal platelet counts that were treated only with paclitaxel. Histologic analysis confirmed the expectation of an increase in tumor apoptosis and a reduction in tumor proliferation in thrombocytopenic mice receiving chemotherapy. No increased toxicity was seen in other organs or blood cells. Taken together, our results indicate that low platelet count selectively induces leakiness of tumor vessels and favors the delivery of chemotherapy to tumor sites, enhancing its tumoricidal effects.
authors.affiliation: The Immune Disease Institute, Boston, Massachusetts 02115, USA.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Demers
authors.forename: Benoit
authors.initials: B
authors.lastname: Ho-Tin-Noé
authors.forename: Daphne
authors.initials: D
authors.lastname: Schatzberg
authors.forename: Janie J
authors.initials: JJ
authors.lastname: Yang
authors.forename: Denisa D
authors.initials: DD
authors.lastname: Wagner
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D018827:Carcinoma, Lewis Lung; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017239:Paclitaxel / Q000493:pharmacokinetics / Q000494:pharmacology*; D013921:Thrombocytopenia / Q000150:complications* / Q000503:physiopathology; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D017239:Paclitaxel