Ovarian Tumor-Stroma Interactions in an In Vivo Orthotopic Model
Abstract
Ovarian cancer spreads by exfoliation or migration. Cell migration is typical of embryonic cells and a few other kinds of normal adult cells, but inappropriate migration is usually suppressed. Consequently, cancer cells must learn how to migrate. One obstacle to migration is the hostility of the microenvironment of the target tissue to epithelial cells of another tissue. Once a cancer cell has migrated to a novel tissue site, it must learn to survive at that site, and part of that process involves modification of the local microenvironment. In this project, we are training ovarian cancer cells to live when in contact with cells from other organs, such as the liver or lung. The goal is to then explore differential gene expression that explains the adaptation of the ovarian cancer cells to the novel environment. We have devised an Intravital Video Microscopy approach to this problem in which MOVCAR cells labeled with green fluorescent protein are embedded in pseudo-organ tissue from a tomato mouse in a small microscopy chamber on dorsal skin fold of a mouse. One problem we encountered was that ovary tissue implanted in the chamber continued to ovulate, and this compromised the clarity of the chamber for microscopy. This was solved by titrating progestin to a high enough dose to prevent ovulation but a low enough dose to allow for MOVCAR tumor growth. We have also found that adaptive changes in gene expression that allow the MOVCAR cells to grow on pseudo-organ tissue persist when the cells are briefly cultured, and we have exploited this for initial gene expression analysis. We are proceeding with high-throughput microdissection and gene expression analysis to study the adaptive gene expression response. This work is important because this model comprises an unusually tractable model for metastasis in which cancer cell gene expression responses to the novel environment can be correlated with real time growth parameters.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2011
- Accession Number
- ADA554643
Entities
People
- Per Borgström