Dr. John Lewis
John Lewis points to a video on his computer screen. In it, hundreds of small cells can be seen winding their way through a blood vessel, seeking a foothold on the surrounding tissue. While small and innocuous now, the cells are deadly. They are cancer.
This movement of tumour cells is part of the process leading up to metastasis, or the spread of cancer from one organ to another. According to Lewis, an associate professor in the University of Alberta's Department of Oncology and the Sojonky Chair in Prostate Cancer Research, it is vital researchers learn more about it.
"We hear a lot about cancer and diagnosis, but really when we think about who succumbs to the disease, 90 per cent of patients who die of cancer have metastasis. So it is metastasis really that is the deadliest aspect of cancer."
The video capture of the spread of tumour cells is an innovation pioneered by Lewis' research team, giving them a window into how the cells move around the body in real time. That technology has now also provided, for the first time, an in-depth look at how the cells attack the tissue from the bloodstream in order to form a new tumour-a process called extravasation. The findings have been published in the Aug. 28 edition of the journal Cell Reports.
Lewis says his team wasn't expecting what they found. "Tumour cells would get stuck in these organs in the blood vessels and they would move around a little bit, and then they would stop and project these little fingers out of the tumour cell."
Those fingers are called invadopodia, and according to Lewis, it's the first time they have been seen in cancer in a live model. The video evidence shows they are necessary for extravasation, as the entire tumour cell eventually follows the invadopodium out of the bloodstream and into the tissue.
"It was one of those eureka moments that you don't get very often," says Lewis. "You cherish it as much as you can."
The findings may hold important implications for the future treatment of cancer. Lewis says his work shows the invadopodia can be inhibited pharmaceutically, stopping tumour cells from escaping the bloodstream and blocking the process of extravasation.
According to Lewis though, the treatments may only have clinical use in very specific situations. Most often, by the time many cancers are diagnosed, metastasis has already occurred in the body and it's too late to prevent extravasation. But the U of A professor says the treatments could be extremely useful if applied during surgical procedures.
"There is emerging evidence, and it's scary evidence, that potentially these procedures can facilitate the spread of [cancer] cells," explains Lewis. "After surgery some cells may be shed off the tumour and be circulated around the blood stream, and evidence suggests that there is an increased chance that these patients may develop metastatic disease somewhere down the road. So there might be a role for these kinds of treatments during surgery or after a biopsy to prevent metastasis."
Lewis says much more study is needed looking into the components of invadopodia, as well as work to develop targeted drugs that can inhibit it without causing broad side effects for the patient.
He believes if there is a chance in the future to cure or block metastasis, fully understanding extravasation is a critical part. A part Lewis hopes his work plays a starring role in. "Hopefully in 20 years, looking back, we'll appreciate how significant [this discovery] is."
FROM THE PAPER regarding funding:
This study was supported by Canadian Cancer Society Research Institute Grant #700537 to Dr. Lewis and an NSERC Discovery Grant to Drs. Lewis and Turley. Dr. Lewis holds the Frank and Carla Sojonky Chair in Prostate Cancer Research supported by the Alberta Cancer Foundation. Dr. Leong was funded by a Canadian Breast Cancer Foundation Post-doctoral Fellowship grant and the Movember Prostate Cancer Canada Rising Stars Grant. Dr. Chambers is Canada Research Chair in Oncology, supported by the Canada Research Chairs Program.