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Pericytes and endothelial precursor cells: cellular interactions and contributions to malignancy
Rebecca G Bagley1, William Weber, Cecile Rouleau
1Genzyme Corp., Framingham, Massachusetts 01701-9322, USA. Rebecca.Bagley@genzyme.com
Cancer Research
|November 4, 2005
Summary
Pericytes and endothelial precursor cells (EPC) promote tumor growth and invasion. While not initiating new blood vessels, these cells may stabilize tumor vasculature and contribute to malignancy.
Area of Science:
- Oncology
- Cell Biology
- Vascular Biology
Background:
- Tumor vasculature is critical for growth, with pericytes and endothelial precursor cells (EPC) playing key roles in angiogenesis.
- In culture, pericytes and EPC exhibit similar angiogenic properties and responses to kinase inhibitors.
- Distinct cell surface markers and molecular profiles differentiate pericytes from EPC.
Purpose of the Study:
- To investigate the role of pericytes and EPC in breast cancer malignancy.
- To compare the characteristics and functions of pericytes and EPC in tumor development.
- To evaluate the potential of pericytes and EPC as models for studying tumor vascularization and therapeutic agent selection.
Main Methods:
- Co-culture assays of MDA-MB-231 breast cancer cells with pericytes or EPC.
- Subcutaneous co-injection of live or irradiated pericytes/EPC with cancer cells in vivo.
- Analysis of tumor growth rates, microvessel density, and immunohistochemical staining of vasculature.
- Assessment of lymphatic vessel formation in tumors.
Main Results:
- Pericytes and EPC enhanced MDA-MB-231 cell invasion in co-culture systems.
- Live pericytes/EPC significantly increased tumor growth rates compared to irradiated cells.
- No difference in microvessel density was observed, but EPC/pericytes appeared to stabilize vasculature.
- Tumors co-injected with EPC showed increased lymphatic vessel development.
Conclusions:
- Pericytes and EPC contribute to cancer malignancy and tumor progression.
- These cells may normalize or stabilize existing tumor vasculature rather than initiate new vessel formation.
- Pericytes and EPC serve as valuable cell-based models for understanding tumor vascular development and identifying therapeutic targets.