The discovery of a mutated fish has led to a breakthrough in understanding how the lymphatic system forms, and could lead to new approaches to curb the spread of cancer.

The research began in 2007 when Professor Ben Hogan found a mutant zebrafish strain, in a genetic screen, while completing his postdoctoral studies in developmental biology at the Hubrecht Institute in The Netherlands.

“I discovered a mutant that formed its blood vessels normally, but did not form its lymphatic vessels,” says Prof Hogan, who is now co-head of Peter Mac’s Program in Organogenesis and Cancer.

The fish had a mutated DDX21 gene which, through Prof Hogan’s research, is now shown to play a fundamental role in forming lymphatic vessels.

A zebrafish, with its vasculature labelled in magenta and the factor at the centre of the findings, Ddx21, labelled in green.
A zebrafish, with its vasculature labelled in magenta and the factor at the centre of the findings, Ddx21, labelled in green.

Prof Hogan and his research collaborators have also mapped the molecular pathway by which the DDX21 gene controls the formation of these vessels.

Critically, understanding the role of this gene (and the pathway it uses) provides a new avenue that could, theoretically, be targeted to curb the spread of cancer.

“Based on our findings, targeting DDX21 would reduce lymphatic vessel formation and growth called lymphangiogenesis,” says Prof Hogan, who is a joint appointment with the Department of Anatomy and Physiology, The University of Melbourne.

“Lymphangiogenesis provides a pathway for the metastatic spread of cancer and reducing it is expected to reduce the burden of metastasis.”

Work is already underway on developing drugs that could inhibit DDX21, which could be tested in disease models.

A paper describing Prof Hogan’s latest research in this space has just been published in the journal Nature Cell Biology.

Read the paper - titled "The RNA helicase Ddx21 controls Vegfc-driven developmental lymphangiogenesis by balancing endothelial cell ribosome biogenesis and p53 function".

And there's an accompanying discussion of this research - "An RNA helicase swirls in lymphangiogenesis".

For more information contact the Peter Mac Communications team on 0417 123 048.

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Peter MacCallum Cancer Centre is a world-leading cancer research, education and treatment centre and Australia’s only public health service solely dedicated to caring for people affected by cancer.