Use of low-molecular-weight heparin to decrease mortality in mice after intracardiac injection of tumor cells

Area of Science:

• Oncology
• Pharmacology
• Animal Models

Background:

• Intracardiac injection in mice is a model for bone metastasis.
• High mortality and neurological signs limit its use with certain human tumor cell lines.
• Tumor cell injection can induce a hypercoagulable state, leading to thromboemboli.

Purpose of the Study:

• To investigate the efficacy of low-molecular-weight heparin (LMWH) in mitigating mortality associated with intracardiac tumor cell injection.
• To determine if LMWH pretreatment preserves the ability to generate bone metastases.
• To expand the utility of the intracardiac injection model for studying diverse tumor cell lines.

Main Methods:

• Establishment of a bone metastasis model via intracardiac injection of human tumor cells in nude mice.
• Administration of intravenous low-molecular-weight heparin (enoxaparin) prior to tumor cell injection.
• Evaluation of mortality rates and assessment of bone metastasis formation.

Main Results:

• Intracardiac tumor cell injection induces a hypercoagulable state, platelet consumption, and thromboemboli.
• Pretreatment with intravenous enoxaparin effectively blocked the hypercoagulable state.
• Enoxaparin pretreatment significantly decreased mortality in mice injected with small-cell lung carcinoma lines (H1975, H2126) while still allowing bone metastasis development.

Conclusions:

• Low-molecular-weight heparin (enoxaparin) is a viable pretreatment to reduce mortality in the intracardiac bone metastasis model.
• This approach broadens the range of tumor cell lines that can be studied.
• The method also contributes to reducing animal usage in metastasis research.