Using intravital microscopy to observe bevacizumab-mediated anti-angiogenesis in human head and neck squamous cell carcinoma xenografts

Abstract

Conclusion: The study showed the value of using intravital microscopy (IVM) analysis for the study of neoangiogenesis. It demonstrated that the model and the analytical methodology could be used to evaluate in detail the effects of treatment strategies for solid tumours. Objectives: Neoangiogenesis is a key component of tumour progression, invasion and metastasis. In clinical trials monoclonal antibodies specific for vascular endothelial growth factor – VEGF (bevacizumab) – have been shown to significantly affect tumour progression when given in combination with standard chemotherapy, and also to improve the overall survival of patients. For squamous cell carcinoma of the head and neck (HNSCC), we still await definitive evidence of the effect of such treatment. The present study was designed to investigate the anti-angiogenesis effect of beviacizumab in green fluorescent protein (GFP)-labelled HNSCC xenografts using IVM technology. Methods: We performed IVM and used image analysis for quantification of angiogenesis and of effects of bevacizumab on cell viability, combined with histochemical and immunohistochemical analysis to standardize the digital analysis of changes in tumour vascularization and cell viability. Results: We found significant effects of bevacizumab on angiogenesis and cancer cell survival in HNSCC. Repeated injections of bevacizumab were found to provide the greatest effects.

Keywords::

• Head and neck cancer
• bevacizumab
• neoangiogenesis
• vascularization

Acknowledgments

This work was supported by the Foundations of Lund University Hospital, the Swedish Cancer Society, the King Gustaf V Jubilee Fund, government funding of clinical research within the NHS, Region of Scania R&D Funding, the Gunnar Nilsson Cancer Foundation, the Mrs Berta Kamprad Foundation for Investigation and Control of Malignant Diseases, and Laryngfonden. We thank Anna Ebbesson and ImaGene–iT AB for technical assistance.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.