Elise Langenkamp

After obtaining a Bachelor’s degree in Pharmaceutical Sciences (2003) and a Master’s degree in Medical and Pharmaceutical Drug Innovation (2005), I started as a PhD student in Medical Sciences at the University of Groningen. My research focussed on blood vessels in tumors and drugs that target these blood vessels in order to deprive tumors from their blood supply and inhibit tumor growth. I defended my thesis just before Christmas 2010 and moved to Uppsala in Sweden to continue my work as a researcher, this time working on blood vessels in brain tumors. We try to understand how certain proteins that are highly expressed in the blood vessels of aggressive high grade gliomas contribute to the development of these primary brain tumors. Because I would like to share the fun of science with others, I am interested in science communication, writing and editing. In addition to spending many hours in the lab, you could find me on the dance floor, where I would be training for competitions in ballroom and latin-american dancing.

PhD thesis

Tumors depend on the formation of new blood vessels to grow beyond a certain size, and to metastasize to other tissues. A key regulator of angiogenesis (neovessel formation) is vascular endothelial growth factor (VEGF). VEGF represents a promising target for antiangiogenic therapy for cancer (the so-called VEGFR2 inhibitors). The design of improved antiangiogenic therapies requires more insight into the molecular nature of the tumor vascular phenotype in vivo of a growing tumor, and of the changes therein in response to therapy.

We characterized the morphology and expression pattern of various angiogenesis‑regulating genes in the vasculature of a melanoma model in different stages of growth, and compared this to the pattern in quiescent non‑angiogenic endothelium from healthy kidneys. This revealed that this tumor type continues to actively engage in angiogenesis during growth using the same specific pro-angiogenic repertoire.

We furthermore investigated how antiangiogenic therapy targeted at VEGFR2 changes the molecular tumor vascular phenotype, and how these changes related to the antitumor effect of the drug. In a lung carcinoma model, treatment with a VEGFR2 inhibitor exerted its antitumor effect by inducing a shift in gene expression toward reduced pro‑angiogenic activity and enhanced vascular stabilization. Yet, in the melanoma model, a different molecular response was underlying the antitumor effect. Moreover, we showed that VEGFR2 inhibitor therapy induced loss of VEGFR2 protein expression in both tumor types. Validation of our findings in clinical tumor specimen is necessary, as therapy‑induced loss of target protein expression may greatly affect efficacy of VEGFR2 inhibitor therapy in the clinic.

A PDF file of the separate chapters or of the complete document can be downloaded from: http://dissertations.ub.rug.nl/faculties/medicine/2010/e.langenkamp/