Researchers at the Burnham Institute for Medical Research (Burnham) may have found a new option for targeted breast cancer therapy by showing the link between a certain protein and the formation and development of blood vessels that feed breast tumors. Like mortar between bricks in a wall, T-cadherin is a protein that helps cells stick together and collectively form tissues. Cancer cells that loosen their adhesive tissue bonds stop producing T-cadherin, and in tumors, only the blood vessels that supply oxygen and nutrients express this protein. Now, Barbara Ranscht, Ph.D., and Robert Oshima, Ph.D., at Burnham have led a team that developed the first living model to study this proteins effect on tumor angiogenesis by creating a strain of mice that develops spontaneous mammary gland tumors in the absence of T-cadherin. Their results appeared March 1 in Cancer Research.
Evidence of T-cadherins role in vascularization has been somewhat controversial, explains Dr. Ranscht, senior author of the study, which includes Drs. Lionel Hebbard and Michle Garlatti from the Burnham Institute as equally contributing first authors and Drs. Robert Cardiff and Lawrence Young as collaborators from the University of California, Davis. But our knockout model clearly shows that T-cadherin plays a role in promoting tumor vascularization, with implications for tumor growth and animal survival.
The tumor model developed in Dr. Ranschts laboratory shows that loss of T-cadherin slows down tumor growth and improves survival compared to controls where T-cadherin is present: The absence of T-cadherin delays tumor growth by an average of 10 days, decreases tumor size, and apoptosis markers, indicators of cell suicide, are six times higher. The tumor-bearing knockouts live an average of 18.5 days longer than their wild-type counterparts, which translates into approximately 18 months of human life span.
The normal models in the study developed solid adenocarcino
|Contact: Andrea Moser|