title: Use of low-molecular-weight heparin to decrease mortality in mice after intracardiac injection of tumor cells.
abstract: Intracardiac injection of human tumor cells into anesthetized nude mice is an established model of bone metastasis. However, intracardiac injection of some human tumor cell lines cause acute neurologic signs and high mortality, making some potentially relevant tumor cell lines unusable for investigation. We showed that intracardiac injection of tumor cells can induce a hypercoagulable state leading to platelet consumption and thromboemboli formation and that pretreatment with intravenous injection of low-molecular-weight heparin (LMWH; enoxaparin) blocks this state. In addition, intravenous injection of enoxaparin before intracardiac injection with 2 different small-cell lung carcinoma lines, H1975 and H2126, dramatically decreased mouse mortality while still generating bone metastases. Therefore, reduction of mortality by pretreatment with LMWH increases the types of cells that can be studied in this metastasis model and decreases the number of animals used.
authors.affiliation: Comparative Animal Research, Amgen Corporation, Seattle, Washington, USA. kstock01@amgen.com
authors.forename: Kim L
authors.initials: KL
authors.lastname: Stocking
authors.forename: Jon C
authors.initials: JC
authors.lastname: Jones
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Everds
authors.forename: Bernard S
authors.initials: BS
authors.lastname: Buetow
authors.forename: Martine P
authors.initials: MP
authors.lastname: Roudier
authors.forename: Robert E
authors.initials: RE
authors.lastname: Miller
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000556:secondary; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D006801:Humans; D007267:Injections / Q000009:adverse effects; D008136:Longevity / Q000187:drug effects*; D008175:Lung Neoplasms / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D013923:Thromboembolism / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight