Investigating the extracellular interactions of the tumour endothelial marker CLEC14A

Khan, Kabir Ali (2016). Investigating the extracellular interactions of the tumour endothelial marker CLEC14A. University of Birmingham. Ph.D.

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Abstract

CLEC14A is an endothelial specific type I transmembrane glycoprotein, which is highly expressed on the vasculature of a wide range of different solid tumours. Identifying extracellular interactions of CLEC14A holds promise for new targets in anti-angiogenic strategies for cancer treatment. CLEC14A directly binds to the extracellular matrix protein multimerin-2 (MMRN2). Both proteins are upregulated with tumour progression and are implicated in endothelial cell function. The CLEC14A-MMRN2 interaction occurs when both proteins are expressed at endogenous levels in endothelial cells, and is dependent upon the C-type lectin domain of CLEC14A. Blocking the CLEC14A-MMRN2 interaction had anti-angiogenic effects and could inhibit the growth of mouse tumour models. Finally, the localisation and targeting of CLEC14A was investigated \(in\) \(vivo\) by use of humanised antibodies and antibody drug conjugates. Data presented in this thesis reinforce the pro-angiogenic functions of CLEC14A and the likelihood of it being a good target for cancer therapy.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):