A key factor in the progression of cancer is its ability to recruit the body’s own blood and lymphatic vessels to provide nutrients and a gateway to spread to other sites. A Peter Mac-led research team has for the first time extensively mapped the signalling networks associated with the specialised cells which line these vessels - endothelial cells.
These cells play an important role not only in cancer progression but also in diverse conditions such as lymphedema, wound healing, transplantation, infectious diseases and inflammation.
“We know these cells are involved when a cancer re-directs the growth of blood vessels and lymphatic vessels to support a tumour’s growth,” says Professor Steven Stacker, Head of the Tumour Angiogenesis and Microenvironment Program at Peter Mac.
“It is these co-opted blood vessels and lymphatic vessels that also give cancer an exit route, allowing it to spread to other sites in the body making it much more difficult to treat.”
“We have now mapped the array of gene-level drivers which determine how these endothelial cells work and can be influenced by cancer, and we hope it will lead to new ways to potentially stop or impede a cancer’s spread.”
The paper – titled Genome-wide functional analysis reveals central signalling regulators of lymphatic endothelial cell migration and remodelling – is published today in the journal Science Signalling.
This study involved the use of a genetic technology that allows the activity of each individual human gene to be examined in endothelial cells, while these cells grow and migrate. This information is then integrated through computer-assisted programs to look at the overall interaction of different genes.
The research may point to new therapeutic targets or, because endothelial cells are also involved in the body’s immune response, ways to boost the effectiveness of an emerging class of immunotherapy drugs. Endothelial cells involved in cancer-related processes also have a unique signature and so it may be possible to create biomarker tests that can detect or predict a cancer’s spread.
“In a typical adult who has cancer there is not much endothelial cell migration occurring apart from what is happening in association with their tumours, so this cellular process could make an effective drug target,” Prof Stacker says.
The lead researchers Dr Steve Williams, Dr Adam Odell and Dr Tara Karnezis, of St Vincent’s Institute’s O’Brien Institute Department, developed the approach in the Tumour Angiogenesis and Microenvironment Program at Peter Mac.
The research also involved major collaborations with Peter Mac Professors Marc Achen and Stephen Fox, and Assoc Prof Kaylene Simpson at the Victorian Centre for Functional Genomics located at Peter Mac, along with scientists at the Doherty Institute and the Walter and Eliza Hall Institute of Medical Research in Melbourne, and Brisbane’s Institute for Molecular Biosciences.