Here's how cancer hijacks wound healing to create its own blood supply

May 01, 2019

Researchers at the University of Virginia School of Medicine have shed light on how cancers hijack the body's natural wound-healing response to grow and spread.

The researchers have identified specific processes within endothelial cells - the cells that line blood vessels - that tumors use to build out their own blood supply. These processes are normally used by the body to repair tissue, heal injuries and grow new blood vessels, but tumors co-opt them to create blood vessels that will nourish them and feed their growth.

"A tumor is not just a ball of malignant cancer cells, right? It's almost like a little miniature organ that creates or co-opts its own blood supply," explained Andrew C. Dudley, PhD, of UVA's Department of Microbiology, Immunology and Cancer Biology. "A tumor steals as it's growing and developing. It steals physiological processes that help it along. And one of those processes is wound healing. And that's what we've been studying - how the tumor subverts this process of wound healing."

Unexpected Diversity

Intriguingly, the research suggests that endothelial cells have a previously unknown degree of specialization that varies among individual cells. Some appear to have a better ability to form new blood vessels than others.

PhD student James V. McCann was able, using some cutting-edge methodologies, to stratify various endothelial cells based on what he called their "functional diversity." This was based partly on the amount of a particular type of microRNA, and the gene it targets, inside the cells. MicroRNAs are tiny molecules responsible for controlling the expression of genes, a process that goes haywire in cancer.

Endothelial cells that were rich in this particular microRNA struggled to sprout new blood vessels, he found, while those with less were better at it. The amount varied even among individual endothelial cells within a developing tumor.

Looking at breast cancer samples, the researchers were able to determine that patients with the best outcomes were those with the highest levels of the microRNA. Further, delivering the microRNA to the endothelial cells of a developing tumor in mice significantly reduced the number of blood vessels and slowed overall tumor growth, McCann found.

The researchers caution that there are obstacles that prevent their work from being immediately applicable in people. Treating breast cancer won't be as simple as giving patients more of this specific microRNA. However, the scientists are excited to have shed light on a vascular-directed process that cancer exploits to create its own blood supply, and to have given scientists new leads in the battle against the disease.

"Cancer as an un-healing wound is an old hypothesis" McCann said. "But we have identified a new way tumors subvert the wound healing process for growth and development."
-end-
The researchers have published their findings in the Journal of Clinical Investigation and was featured on the cover. The research team consisted of McCann, Lin Xiao, Dae Joong Kim, Omar F. Khan, Piotr S. Kowalski, Daniel G. Anderson, Chad V. Pecot, Salma H. Azam, Joel S. Parker, Yihsuan S. Tsai, Alisa S. Wolberg, Stephen D. Turner, Kohei Tatsumi, Nigel Mackman and Dudley. Anderson disclosed that he has a patent related to the work.

The research was supported by the National Institutes of Health, including grants RO1-CA177874 and P30-CA14051; the American Cancer Society, grant 129755-RSG-16-176-01-DDC; and an AACR-Bayer Innovation and Discovery Grant, 17-80-44-DUDL. In addition, the work was partially supported by the U.S. Army Medical Research and Materiel Command's Armed Forces Institute of Regenerative Medicine, grant W81XWH-08-2-0034.

To keep up with the latest medical research news from UVA, subscribe to the Making of Medicine blog at http://makingofmedicine.virginia.edu.

University of Virginia Health System

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.