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09:03
Modified In Vivo Matrix Gel Plug Assay for Angiogenesis Studies
Published on: June 30, 2023
In vivo modulation of angiogenesis by beta 2 glycoprotein I
1Department of Immunology, Allergy and Infectious Disease, University of New South Wales, St. George Hospital, 2 South St., Kogarah, NSW 2217, Sydney, Australia.
Journal of Autoimmunity
|July 27, 2010
Summary
Beta 2 glycoprotein I (β2GPI) acts as an anti-angiogenic factor in vivo, but its function is altered by angiogenic stimuli. Its absence enhances tumor growth and microvessel density, though it doesn't impact tumor cell proliferation.
Area of Science:
- Immunology
- Angiogenesis Research
- Oncology
Background:
- Beta 2 glycoprotein I (β2GPI) is a key autoantigen in antiphospholipid syndrome.
- β2GPI interacts with proteins involved in fibrinolysis and angiogenesis.
- Its role in angiogenesis requires further in vivo investigation.
Purpose of the Study:
- To investigate the in vivo angiogenic potential of β2GPI.
- To utilize β2GPI deficient mice for angiogenic assays.
- To determine β2GPI's effect on tumor growth and angiogenesis.
Main Methods:
- Angiogenic assays using growth factor-free and bFGF-containing matrigel implants in β2GPI deficient mice.
- Measurement of hemoglobin content in VEGF-containing matrigel plugs.
- Assessment of Melanoma B16F10 tumor growth and microvessel density in β2GPI deficient mice.
- Ki67 immunohistochemistry for tumor cell proliferation.
- Subcutaneous delivery of human β2GPI via osmotic pump.
Main Results:
- β2GPI deficient mice showed increased microvessel formation in growth factor-free matrigel.
- Microvessel formation was reduced in β2GPI deficient mice with bFGF compared to controls.
- VEGF-induced extravasation (hemoglobin content) was higher in β2GPI deficient mice.
- Melanoma tumor growth and microvessel density were enhanced in β2GPI deficient mice.
- Tumor cell proliferation and tumor growth were unaffected by β2GPI administration in deficient mice.
Conclusions:
- The unopposed action of β2GPI is anti-angiogenic in vivo.
- Strong angiogenic stimuli modify β2GPI's function towards vessel stabilization.
- While β2GPI can attenuate vessel sprouting in some tumors, it does not confer a survival benefit.
- Modified β2GPI or its fragments may hold potential for anti-angiogenesis therapies.
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