Biological Mechanisms of Metastasis Suppression: Which Steps in the Metastatic Cascade are Inhabited by the Metastasis Suppressor Gene BRMS1?
Annual summary rept. 1 Jun 2002-31 May 2005
LONDON REGIONAL CANCER CENTRE (ONTARIO)
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The purpose of this research is to determine which steps in the metastatic process are affected by the metastasis suppressor gene, BRMS1. Stable b-Gal expressing MDA-MB-231 and MDA-MB-231BRMS1 cell lines were used to identify 2 steps in the metastatic process inhibited by BRMS1. It was found that BRMS1-expression I reduced the numbers of solitary cells that survive initial arrest in the lung 4 hours and 2 reduced the numbers of cells that initiate form microscopic lung metastases 4 weeks both p 0.05. Both these decreases account for the 80 reduction in lung metastases seen after 8 weeks. In vitro work has shown that anchorage dependence may account of the reduction seen after 4 hours and work is underway to determine factors that may be responsible for the growth inhibition. To determine if BRMS1 suppresses metastatic growth in liver, BRMS1 over-expressing cells and controls were injected via the mesenteric vein to target the liver. No suppression of liver metastases was seen by BRMS1 expression in MDA-MB-435 breast cancer cells. To date these studies have shown no significant difference between the growth rates and vascularity assessed by HE and CD31 of MDA-MB-435 - BRMS1 primary tumors in nude mice. However, a significant lag in initial tumor detection in BRMS1-expressing MDA-MB-435 cells was observed. Furthermore, a significant reduction in the numbers of functional vessels in BRMS1-expressing primary tumors has been shown and work in progress will determine the extent of this reduction.
- Anatomy and Physiology