Dr. Valerie LeBleu, Ph.D., a Harvard trained researcher in Cancer Biology and an Assistant Professor in Department of Cancer Biology at MD Anderson, just published an important study that could have significant impacts on future therapeutic drug targets for the treatment of breast cancer (BC). The study entitled “Targeting Vascular Pericytes in Hypoxic Tumors Increases Lung Metastasis via Angiopoietin-2” was published in the current on-line edition of Cell Reports.
- Metastasis: when cancer spreads from the tumor of origin, known as the primary tumor, to a secondary location within the body
- Angiogenesis: the growth of blood vessels from existing vessels- cancerous tumors release proteins, known as angipoietins, that stimulate angiogenesis and allow the malignant tumor to have a rich blood supply
- Pericytes: cells that play an important role in maintaining the stability of blood vessel tissue structure
With the understanding that metastatic cancerous tumors must have a steady flow of blood to emerge and spread, Dr. LeBlue, and her team of collaborative investigators studied the role that a specific angipoietin, angiopoietin-2 (ANG2) in combination with a pericyte depletion, had on the growth of BC tumors in a mouse model.
The study findings showed the following
- The number of pericytes surrounding a vessel changes dramatically during tumor progression
- Targeting pericytes increases oxygen depletion within a tumor and lung metastasis
- Defects in pericyte-depleted vessels are mediated by ANG2 uptake
- ANG2 blocking stabilizes tumor vessels and reduces metastasis
In a recent press release, Dr. LeBlue commented on the experimental results, stating, “Our study showed that angipoietin signaling is a key metastasis promoting pathway associated with abnormal tumor blood vessels with poor pericytes coverage. When combined with pericyte loss during the late phases of tumor progression, it is possible to reduce both primary tumor growth and metastatic disease.”
This study adds to the growing body of knowledge showing the important role pericytes play in angiogenesis by providing important insights into the specific mechanisms that pericyte/ANG2 interaction has on metastasis. This knowledge could potentially make it possible for ant-ANG2 targeting drugs that control metastasis, to be developed in the future.
In a comment explaining the contribution these findings may have on future research, Dr. LeBlue said, “Targeting of ANG2 signaling in tumors with abnormal blood vessels with low pericyte coverage appeared to restore vascular stability and decreased tumor growth and metastasis in lung cancer mouse models. We also found that ANG2 was tied to poor outcome in patients with breast cancer. These results emphasize the potential for therapies targeting advanced tumors with poor quality blood vessels.”