Quantitative Analysis of Breast Cancer Metastasis to the Brain

Date
2009-05
Journal Title
Journal ISSN
Volume Title
Publisher
University of Delaware
Abstract
Previous experiments have shown that MDA-MB-231 human breast cancer cells could be injected into the extra-embryonic vasculature of chick embryos, and then cells which had metastasized to the brain could be isolated by drug selection. The sensitivity of the in vivo chick embryo system was tested by initially injecting embryos with a large number of cells (5x104) and then decreasing the number of cells injected tenfold to see if tumors would still form. Injections of 5x104 MDA-MB-231 cells produced an average of 186.6 colonies after treatment with G418, and injections 5x103 cells produced an average of 37.1 colonies. Experiments with nude mice have shown that re-injecting MDA-MB-231 cells which have been through the brain produced sublines with enhanced capacity to metastasize to the brain. In order to assess the effects of re-injection on cells, colony analysis was performed on serially injected cells. It was found that the average number of colonies detected decreased as cells were injected and recovered from the brain multiple times. It is speculated that the smaller colony numbers are due to cells dividing slower and forming smaller tumors, and not necessarily fewer cells extravasating to the brain, and re-injected cells are possibly entering a state of dormancy. Although I was not able to demonstrate that serial injection into chick embryos resulted in a brain-specific subline, as similar experiments did in previous mouse studies, this study has shown that the chick embryo is a useful model system for studying breast cancer metastasis to the brain. It has proven to be a sensitive system, as injection of only 5x103 cells resulted in measurable brain metastases. This system, along with colony analysis, will be useful for studying the effects of the manipulation of protein expression on metastatic capability in order to gain an understanding of the molecular mechanisms of metastasis.
Description
Keywords
Citation