Researchers at the Burnham Institute for Medical Research have identified a protein that may be associated with the formation and development of blood vessels that feed breast tumours.
T-cadherin is a protein that helps cells stick together and collectively form tissues. Only the blood vessels that supply oxygen and nutrients express this protein.
AdvertisementLead researchers Barbara Ranscht, and Robert Oshima, focussed their study on the protein's effect on tumour progression.
"Evidence of T-cadherin's role in vascularization has been somewhat controversial," said Dr. Ranscht.
"But our knockout model clearly shows that T-cadherin plays a role in promoting tumour vascularization, with implications for tumour growth and animal survival," she added.
The researchers conducted their study using mice model with spontaneous mammary gland tumours developed in the absence of T-cadherin.
The findings revealed that absence of T-cadherin protein inhibited tumour growth and improved survival compared to controls where T-cadherin is present.
The loss of T-cadherin delays tumour growth by an average of 10 days, decreases tumour size, and apoptosis markers, indicators of cell suicide, are six times higher.
The tumour-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.
"Stunting blood vessel growth restricts tumours and prolongs survival-a strategy behind anti-angiogenesis cancer drugs like Avastin-so these results were somewhat expected," said Dr. Ranscht.
"But what surprised us was that even though our models survived longer, their tumour pathology worsened," she added.
Without T-cadherin-mediated vascularization, breast cancer cells consistently metastasized to the lungs, and this did not happen in the control mice where the tumours were highly vascularized.
This study also showed for the first time in a living model that T-cadherin is essential for binding adiponectin, a hormone produced by fatty tissue that is released in inversely proportional amounts to body fat.
Adiponectin has a protective effect against metabolic diseases including diabetes, hypertension, heart disease, and stroke; now for the first time it is linked in a living model with vascular function.
"While the link between obesity and breast cancer is complex, this study shows that in the mouse, T-cadherin sequesters much of the adiponectin and thus provides a conceptual link between obesity and breast cancer," said Dr. Oshima.
The study appears in journal Cancer Research.
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