Date of Completion
CD13, Tumor Vasculature
Linda H Shapiro, PhD
Field of Study
Doctor of Philosophy
Optimal tumor growth relies on the integration of inflammation and angiogenesis such that a number of molecules are critical regulators of both processes contributing to the overall orchestration of cancer growth and progression. The cell-surface peptidase CD13 is expressed on myeloid cells and activated endothelium where it acts as both a homotypic adhesion molecule regulating inflammatory myeloid cell migration and a regulator of angiogenesis. Naïve wild type or CD13-deficient mice showed identical baseline immune profiles, but displayed significant differences in the number and ratio of myeloid subsets recruited to sites of ischemic injury as well as effects on angiogenesis, prompting our investigation into the contribution of CD13 to angiogenesis and inflammation in tumors. Surprisingly, and in contrast to injury models, tumor allografts grown in CD13-deficient mice were larger and showed increased numbers of infiltrating monocytes, dendritic cells and macrophages resulting in increased levels of inflammatory and angiogenic cytokines. Paradoxically, the capillary density of these larger tumors in CD13-deficient animals was markedly decreased with significant improvement in the percentage of blood vessels stabilized by pericytes, suggesting CD13 contributes to dysregulated tumor angiogenesis. Mechanistically, the junctional localization of VE-cadherin was significantly enhanced in endothelial monolayers treated with CD13 blocking antibodies, which would predict improved pericyte-endothelial contacts in vivo. Therefore, this work illustrates that loss of CD13 contributes to immune cell infiltration and angiogenesis to promote solid tumor progression identifying CD13 as a novel target for normalization of tumor blood vessels, a contemporary therapeutic goal in tumor treatment.
CD13 Destabilizes Vasculature in Tumors
Kaitlyn Margaret Vernier B.S. Randolph-Macon College
Ph.D. University of Connecticut
Directed by: Linda H Shapiro Ph.D.
Vernier, Kaitlyn M., "CD13 Destabilizes Vasculature in Tumors" (2013). Doctoral Dissertations. 187.