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Screening of angiogenesis inhibitors by modified tumor-induced angiogenesis (TIA) test in lung cancer
E Skopińska-Rózewska1, E Sommer, U Demkow
1Department of Immunology, Surgery, National Institute of Tuberculosis and Lung Diseases, Warsaw.
Abstract:
Aberrant angiogenesis-the new vessels formation is a mandatory event in the process of tumor growth and expansion. Studies on mechanisms involved in tumor-induced angiogenesis (TIA) and on its possible inhibitors are needed in order to introduce in future new methods of tumor treatment. The aim of our study was to determine the usefulness of the modified cutaneous TIA (mice without immunosuppression) test for screening in vivo of the angiogenesis modifiers. In both models (classical and modified TIA) we demonstrated comparable angiogenesis activity following human lung cells inoculation and similar degree of neovascularization response inhibition caused by theobromine. We reported that in modified TIA model preincubation with theobromine significantly suppressed angiogenic potential of human lung cancer cells as well as the ability of those cells to produce proangiogenic cytokine-bFGF.
Insights
This study validates a modified angiogenesis test for screening tumor treatment inhibitors. Theobromine effectively suppressed tumor cell angiogenesis and proangiogenic factor production in this model.
Area of Science:
- Oncology
- Vascular Biology
- Pharmacology
Background:
- Aberrant angiogenesis, the formation of new blood vessels, is crucial for tumor growth and expansion.
- Understanding tumor-induced angiogenesis (TIA) mechanisms and identifying inhibitors are vital for developing novel cancer therapies.
- The classical TIA model requires immunosuppression, limiting its applicability.
Purpose of the Study:
- To evaluate the utility of a modified cutaneous TIA test (without immunosuppression) for in vivo screening of angiogenesis modifiers.
- To compare the efficacy of the modified TIA model with the classical TIA model.
- To assess the inhibitory effects of theobromine on angiogenesis and related factors.
Main Methods:
- Development and application of a modified cutaneous TIA model using mice without immunosuppression.
- Comparison of angiogenesis activity and neovascularization response inhibition between classical and modified TIA models.
- Assessment of theobromine's effect on the angiogenic potential and bFGF production of human lung cancer cells in the modified TIA model.
Main Results:
- Both classical and modified TIA models demonstrated comparable angiogenesis activity upon human lung cell inoculation.
- Theobromine exhibited a similar degree of neovascularization response inhibition in both TIA models.
- Preincubation with theobromine in the modified TIA model significantly suppressed the angiogenic potential of human lung cancer cells.
- Theobromine also inhibited the production of the proangiogenic cytokine, basic fibroblast growth factor (bFGF), by these cells.
Conclusions:
- The modified cutaneous TIA test is a useful tool for in vivo screening of angiogenesis modifiers without the need for immunosuppression.
- Theobromine demonstrates significant anti-angiogenic properties by suppressing tumor cell angiogenic potential and bFGF production.
- This modified TIA model provides a valuable platform for preclinical evaluation of novel anti-cancer agents targeting angiogenesis.