2 min readStudy Shows Tumour Cells that Mimic Blood Vessels Could Help Breast Cancer Spread to Other Sites

Cold Spring Harbor, NY — A team of researchers from Cold Spring Harbor Laboratory (CSHL) and the CRUK Cambridge Institute at the University of Cambridge has shown in a mouse model that the ability of tumour cells to form tubular networks that mimic blood vessels can help drive metastasis, the spread of breast cancer to different sites in the body.

The team has discovered that two genes, Serpine2 and Slpi, help direct a phenomenon known as “vascular mimicry.” Vascular mimicry involves the formation of tubular networks made of tumour cells, which can transport blood to different parts of a tumour. These tubular networks are thought to be able to provide the tumour with oxygen and nutrients, thus mimicking the role of blood vessels. The researchers found that reducing the expression of Serpine2 or Slpi in a primary tumour reduced vascular mimicry in the tumour.

The team was led by CSHL Professor and HHMI investigator, Gregory Hannon, who is also a Professor at the Univeristy of Cambridge and by Simon Knott, a research investigator at CSHL. CSHL postdoctoral researcher Elvin Wagenblast is the first author of the report announcing the findings today in Nature.

Vascular mimicry appears also to allow tumour cells greater access to the bloodstream, from where they can spread to other sites in the body. Overexpressing Serpine2 or Slpi led to more tumour cells being able to get into the blood. These same genes have previously been found to be overexpressed in human patients whose cancers had spread to their lungs.

“It’s very neat to watch and see cells evolve to have these capacities,” says Knott. “But on the other hand it’s really scary to think that these cells are sitting there in people doing this.”

The fact that the products of the genes in question, Serpine2 and Slpi, are secreted proteins means that they are both potentially targetable. That’s something the researchers are looking into. “Targeting them might provide therapeutic benefits, but we’re not sure yet,” says Knott. Targeting these proteins could prevent tumour cells from exiting a secondary site and spreading further.

In past years, efforts have been made to treat tumours by using drugs called angiogenesis inhibitors that curb the formation of new blood vessels, as tumours need blood vessels to grow and spread. These drugs have not been as successful as hoped in patients, and one reason could be because vascular mimicry kicks in to help tumours get nutrients and oxygen, speculates Wagenblast. “Maybe by targeting angiogenesis and also vascular mimicry at the same time we might actually have a better benefit in the clinic in the long run,” he says.

The researchers are now examining what it takes for tumour cells that have exited from a primary tumour into the bloodstream to then get out of the bloodstream and colonize a new site in the body. “We’ve identified some interesting targets that we think seem to be key for this step,” Knott says.

Article adapted from a Cold Spring Harbor Laboratory news release.

Publication: A model of breast cancer heterogeneity reveals vascular mimicry as a driver of metastasis. Elvin Wagenblast, Mar Soto, Sara Gutiérrez-Ángel, Christina A. Hartl, Annika L. Gable, Ashley R. Maceli, Nicolas Erard, Alissa M. Williams, Sun Y. Kim, Steffen Dickopf, J. Chuck Harrell, Andrew D. Smith, Charles M. Perou, John E. Wilkinson, Gregory J. Hannon, Simon R. V. Knott. Nature (2015): Click here to view.

 

Oncogenomics

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