Ovarian Tumor-Stroma Interactions in an In Vivo Orthotopic Model
Annual rept. 20 Jul 2011-19 Jul 2012
VACCINE RESEARCH INST OF SAN DIEGO CA
Pagination or Media Count:
The objective of this project is to develop a syngeneic orthotopic intravital video microscopy method to study ovarian cancer. In this model, MOVCAR cells are implanted on minced, revascularized ovary tissue in a dorsal skinfold chamber and allowed to grow. The most informative strategy has been to serially implant such tumors from mouse to mouse, and follow gene expression. In other experiments, this strategy yields a time course of adaptive responses to the novel environment. With the MOVCAR-pseudo-ovary model, we encountered problems of chamber clouding due to bleeding due to ovulation, which we overcame by titrating progestin in the hosts diet, and toxicity of mCherry, which we overcame by switching to GFP. We are now wrestling with the problem that the MOVCAR cells lose their ability to grow in vitro, for which there are two possible solutions, one relying on the stochasticity of loss of growth in vitro, and the other involving co-evolution of growth in vivo and growth in vitro. We have made substantial progress in developing an algorithmic approach to these adaptive data.
- Medicine and Medical Research