Preventing Development of New Blood Vessels Generates More Aggressive Tumors

Cancer researchers created a mouse model that they used to study the role of the calcium-dependent cell adhesion glycoprotein T-cadherin on the development and spread of breast cancer.

Investigators at the Burnham Institute for Medical Research (La Jolla, CA, USA) created a strain of "knockout” mice that developed spontaneous mammary gland tumors in the absence of T-cadherin. They reported in the March 1, 2008, edition of the journal Cancer Research that absence of T-cadherin delayed tumor growth by an average of 10 days, decreased tumor size, and apoptosis markers--indicators of cell suicide--were six times higher than in control mice with normal amounts of T-cadherin. The tumor-bearing knockout mice lived an average of 18.5 days longer than the wild-type controls. Despite their reduced ability to generate new blood vessels, T-cadherin-deficient tumors were pathologically advanced and metastasized to the lungs.

"Evidence of T-cadherin's role in vascularization has been somewhat controversial,” explained senior author Dr. Barbara Ranscht, professor of neurosciences at the Burnham Institute. "But our knockout model clearly shows that T-cadherin plays a role in promoting tumor vascularization, with implications for tumor growth and animal survival. But what surprised us was that even though our models survived longer, their tumor pathology worsened. Without T-cadherin-mediated vascularization, breast cancer cells consistently metastasized to the lungs, and this did not happen in the control mice where the tumors were highly vascularized.”

While the reason for the higher level of tumor vascularization in the knockout mice was not elucidated, Dr. Ranscht warned that, "Our work provides a cautionary example that restricting tumor angiogenesis might result in more aggressive disease in the long run. Thus, anti-antigenic therapies should be carefully evaluated, because if growth at the primary tumor site slows but at the same time women develop more aggressive, metastatic cancers, then it is imperative to develop and add treatments that prevent this.”


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Burnham Institute for Medical Research