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Monitoring Functionality and Morphology of Vasculature Recruited by Factors Secreted by Fast-growing Tumor-generating Cells
Published on: November 23, 2014
Characterization of the effects of antiangiogenic agents on tumor pathophysiology
B M Fenton1, B K Beauchamp, S F Paoni
1Department of Radiation Oncology, University of Rochester Medical Center, Rochester, New York 14642, USA.
Abstract:
A variety of strategies have been proposed to control tumor growth and metastasis by inhibiting tumor angiogenesis. To optimally combine such antiangiogenic approaches with conventional therapy, improved methods are needed to characterize the underlying pathophysiologic changes. The objective of the current work was to demonstrate the utility of a combination of recently developed immunohistochemical and image analysis techniques in quantitating changes in tumor vasculature and hypoxia. Murine MCa-35 mammary carcinomas were frozen after administration of two COX-2 inhibitors: meloxicam and celecoxib (Celebrex). Total blood vessels were visualized using anti-CD31 staining, perfused vessels by intravenous injection of DiOC7, and tumor hypoxia by EF5 uptake. Although both agents produced similar reductions in tumor volume compared with untreated tumors, varied effects on tumor vasculature and hypoxia were noted. Meloxicam reduced total vessel numbers significantly, whereas celecoxib had no effect. Both drugs substantially increased perfused vessel densities. Although mean hypoxic marker uptake was unchanged from matched controls, intratumor EF5 heterogeneities were significantly different between drugs. The results suggest that COX-2 inhibitors can have varying effects on tumor pathophysiology. Successful use of these drugs to enhance radiation response will likely require optimization of drug choice, dose schedule, and direct physiologic monitoring.
Insights
Two COX-2 inhibitors reduced tumor volume but had different effects on tumor vasculature and hypoxia. Optimizing these drugs for cancer therapy requires monitoring their specific physiologic impacts.
Area of Science:
- Oncology
- Pharmacology
- Biomedical Imaging
Background:
- Tumor growth and metastasis can be controlled by inhibiting tumor angiogenesis.
- Optimal combination of antiangiogenic therapies with conventional treatments requires better characterization of pathophysiologic changes.
- Cyclooxygenase-2 (COX-2) inhibitors are being investigated for their antiangiogenic potential in cancer therapy.
Purpose of the Study:
- To demonstrate the utility of combined immunohistochemical and image analysis techniques for quantifying changes in tumor vasculature and hypoxia.
- To compare the effects of meloxicam and celecoxib (Celebrex) on tumor pathophysiology.
Main Methods:
- Murine MCa-35 mammary carcinomas were treated with meloxicam or celecoxib.
- Tumor vasculature was assessed using anti-CD31 staining (total vessels) and DiOC7 injection (perfused vessels).
- Tumor hypoxia was measured by EF5 uptake, and image analysis quantified changes.
Main Results:
- Both meloxicam and celecoxib reduced tumor volume similarly.
- Meloxicam significantly reduced total vessel numbers, while celecoxib had no significant effect.
- Both drugs increased perfused vessel densities, but induced different patterns of tumor hypoxia heterogeneity.
Conclusions:
- COX-2 inhibitors exhibit varied effects on tumor pathophysiology, impacting vasculature and hypoxia differently.
- Successful application of these agents to enhance conventional therapies like radiation likely necessitates tailored drug selection, dosage, and scheduling.
- Direct physiologic monitoring is crucial for optimizing the use of COX-2 inhibitors in cancer treatment.
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