The effect of cancer cells on angiogenesis: engineering the cancer niche (676.13)

Abstract

Tumor growth requires uncontrolled angiogenesis, defined as the growth of new capillaries from existing blood vessels. Developing anti‐tumor therapies necessitates understanding how cancer cells and their microenvironment synergistically influence capillary sprouting from existing vascular networks. Recently, we demonstrated the use of the rat mesentery culture model for investigating angiogenesis in an intact microvascular network scenario. The objective of this study was to demonstrate the use of this model to determine the effects of cancer cells on angiogenesis. Mesenteric tissue windows were harvested from adult male Wistar rats and cultured for 5 days according to the following experimental groups: 1) Control (MEM + 10% DMEM + 1% FBS; n = 7 tissues) and 2) Cancer Cell (MEM + 10% DMEM + 1% FBS + cells; n = 6 tissues). For the cancer cell group, 2x10^5 RFP‐transfected metastatic MDA‐MB‐231 breast cancer cells were seeded onto tissues on day 0. On day 5, cancer cells remained viable, as confirmed by live/dead assay. More importantly, cells were observed to be in the same focal plane and region as vessels along intact microvascular networks. The presence of cancer cells decreased vascular length density and the number of capillary sprouts per vascular area compared to the Control (no cell) group. Our results suggest that cancer cells alone are not sufficient to induce angiogenesis. Application of the rat mesentery culture model as a multicellular breadboard system to engineer the cancer cell/vascular niche will offer a new tool for tumor angiogenesis research.Grant Funding Source: Supported by Tulane Center for Aging and NIH 5‐P20GM103629‐02