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Differential growth inhibition of cerebral metastases by anti-angiogenic compounds
Daniel K Martin1, Ortrud Uckermann1, Aiko Bertram1
1Department of Neurosurgery, Carl Gustav Carus University Hospital, Dresden University of Technology, Dresden, Germany.
Background:
The formation of brain metastases is intrinsically linked to concomitant angiogenesis. The purpose of the present study was to investigate the combined effects of interleukin-12 (IL-12) and EMD121974 on the growth and distribution of melanoma brain metastases since both substances may interact with important steps in the cascade of brain metastases formation.
Materials And Methods:
Brain metastases were induced by either stereotactic implantation of cells to the brain parenchyma or by injection of the melanoma cells into the internal carotid artery to mimic hematogenous metastatic spread in mice. Naive or IL-12-overexpressing murine K1735 melanoma cells were used either alone or in combination with intraperitoneal anti-integrin treatment using EMD121974.
Results:
Solid melanoma metastases were more susceptible to daily low-dose treatment of EMD121974 than multiple hematogenous metastases. Interleukin-12 had a profound effect on both types of brain metastases. After 21 days, a marked reduction of vascularity was observed in both tumor types.
Conclusion:
The combination of endogenous IL-12 production with integrin blockade resulted in additive effects for murine hematogenous brain metastases but not for focal brain metastases.
Insights
Interleukin-12 (IL-12) and EMD121974 combination therapy showed additive effects on murine hematogenous brain metastases. This combination reduced vascularity in both focal and hematogenous melanoma brain metastases.
Area of Science:
- Oncology
- Cancer Metastasis
- Angiogenesis
Background:
- Brain metastasis formation is closely linked to angiogenesis.
- Interleukin-12 (IL-12) and EMD121974 are investigated for their roles in brain metastasis.
- Both agents may influence critical steps in brain metastasis development.
Purpose of the Study:
- To investigate the combined effects of IL-12 and EMD121974 on melanoma brain metastases growth and distribution.
- To understand the interaction of these agents in the brain metastasis cascade.
Main Methods:
- Murine K1735 melanoma cells were used, with or without IL-12 overexpression.
- Brain metastases were induced via stereotactic implantation or internal carotid artery injection.
- Mice received intraperitoneal anti-integrin treatment with EMD121974.
Main Results:
- EMD121974 daily low-dose treatment was more effective against solid melanoma metastases than multiple hematogenous ones.
- IL-12 significantly impacted both focal and hematogenous brain metastases.
- Marked reduction in vascularity was observed in both tumor types after 21 days.
Conclusions:
- Combining endogenous IL-12 production with integrin blockade (EMD121974) yielded additive effects for murine hematogenous brain metastases.
- This combination did not show additive effects for focal brain metastases.
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