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Published on: January 19, 2018
Effect of antiangiogenic therapy on slowly growing, poorly vascularized tumors in mice
W D Beecken1, A Fernandez, A M Joussen
1Department of Surgery, Children's Hospital, and Harvard Medical School, Boston, MA, USA.
Background:
Angiogenesis is essential for tumor growth and progression. Therefore, inhibition of angiogenesis is being studied as a new anticancer therapy. Because cytotoxic chemotherapy is more effective on rapidly growing tumors than on slowly growing tumors, it has been assumed that antiangiogenic therapy will also be effective only on rapidly growing, highly vascularized tumors. We compared the effects of two angiogenesis inhibitors, TNP-470 and angiostatin, on slowly growing, poorly vascularized and rapidly growing, highly vascularized human tumors in mice.
Methods:
Slowly growing (RT-4) and rapidly growing (MGH-U1) human bladder carcinoma cell lines were grown in severe combined immunodeficiency mice. Established tumors were treated with one of the two angiogenesis inhibitors. Tumor volumes, vascularity, and proliferation indices were determined. The in vitro effects of TNP-470 and of angiostatin on the proliferation of RT-4 and MGH-U1 cells were also investigated. All statistical tests were two-sided.
Results:
RT-4 and MGH-U1 tumor growth was statistically significantly inhibited by both angiogenesis inhibitors (P<.001). Both inhibitors decreased the blood vessel density in both tumor types but did not alter the in vivo proliferation indices of the tumors. TNP-470, but not angiostatin, marginally decreased the in vitro proliferation of MGH-U1 cells.
Conclusion:
Slowly growing, poorly vascularized tumors in animal models respond as well as rapidly growing, highly vascularized tumors to therapy with the angiogenesis inhibitors TNP-470 and angiostatin.
Insights
Angiogenesis inhibitors TNP-470 and angiostatin effectively treat both slow-growing and fast-growing tumors. This challenges the assumption that antiangiogenic therapy is only effective on highly vascularized tumors.
Area of Science:
- Oncology
- Cancer Biology
- Vascular Biology
Background:
- Angiogenesis is crucial for tumor growth and progression.
- Inhibition of angiogenesis is a promising anticancer strategy.
- Current assumptions suggest antiangiogenic therapies are most effective against rapidly growing, highly vascularized tumors.
Purpose of the Study:
- To compare the efficacy of two angiogenesis inhibitors, TNP-470 and angiostatin.
- To evaluate their effects on both slowly growing, poorly vascularized tumors and rapidly growing, highly vascularized tumors.
- To investigate the impact of these inhibitors on tumor growth, vascularity, and proliferation.
Main Methods:
- Human bladder carcinoma cell lines (slowly growing RT-4, rapidly growing MGH-U1) were xenografted into immunodeficient mice.
- Established tumors were treated with TNP-470 or angiostatin.
- Tumor volume, vascularity, proliferation indices, and in vitro cell proliferation were assessed.
Main Results:
- Both TNP-470 and angiostatin significantly inhibited tumor growth in both models (P<.001).
- Vascular density was reduced by both inhibitors, without altering in vivo proliferation.
- TNP-470 showed a marginal decrease in in vitro MGH-U1 cell proliferation, while angiostatin did not.
Conclusions:
- Slowly growing, poorly vascularized tumors respond comparably to rapidly growing, highly vascularized tumors.
- Angiogenesis inhibitors TNP-470 and angiostatin demonstrate broad efficacy across different tumor growth rates and vascularization levels.
- These findings challenge existing paradigms regarding the selective applicability of antiangiogenic therapies.
