25 October 2007
Novel drugs could starve breast tumors of blood supply
MedWire News: Scientists have discovered a novel molecular mechanism that breast tumors use to initiate angiogenesis and maintain a blood supply.
The researchers hope that new treatments could target this pathway and combat metastatic spread in breast cancer.
The onset of vascularization, referred to as the "angiogenic switch," supplies a nascent tumor with the nutrients and oxygen it requires for growth, explain Ian Buxton (University of Nevada, Reno, USA) and colleagues in the British Journal of Cancer.
In fact, tumors in a pre-vascularized state are unable to grow beyond 2-3mm3 in size because a balance between active proliferation and apoptosis keeps them in an arrested state of growth, they add.
One factor, nucleoside diphosphate kinase (NDPK), has recently emerged as a potential player in angiogenesis. Expression of NDPK is a marker of metastasis and cells have been observed to secrete the protein into their surrounding environment in vitro.
In the present study, Buxton et al cultured vascular endothelial cells in vitro and observed the rate of angiogenesis based on the formation of tube-like structures.
Angiogenesis scores were calculated by multiplying the mean number of branch points by the mean branch length and by mean cell surface area.
When the researchers treated these endothelial cells with NDPK they observed a 70% increase in angiogenesis relative to untreated cells.
Noting that the P2Y endothelial receptor is a potential target of NDPK, the researchers treated endothelial cells with a P2Y receptor antagonist in the presence of NDPK and found that angiogenesis was suppressed back to levels seen in control cells.
Based on these and other findings, the researchers propose a model whereby cancer cells secrete NDPK into the extracellular environment, which then docks with P2Y receptors on the endothelial surface stimulating tumor angiogenesis.
The researchers speculate that novel therapies that target this pathway could be developed to prevent angiogenesis and inhibit tumor growth.
"Since women who succumb to breast cancer have often undergone surgery to remove the primary tumor, anti-angiogenic therapies may be considered essential in combating the metastatic spread often seen years later," conclude Buxton et al.
Br J Cancer 2007; Advance online publication
http://www.nature.com/bjc/index.html
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