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How Vesicles Secreted by Cells Aid Cancer Growth

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Dolores Di Vizio, MD, PhD

In a recently published study, a Cedars-Sinai team led by Dolores Di Vizio, MD, PhD, associate professor of Surgery, Pathology and Laboratory Medicine and Biomedical Sciences, demonstrated that large oncosomes contribute to tumor growth. The team also identified the molecular mechanism by which large oncosomes play a role in communication between prostate tumors and the surrounding tissue.

These findings suggest potential ways to identify aggressive forms of prostate cancer early in the disease process and block the spread of cancer. The findings also propose a new targetable mechanism — large oncosomes-mediated communication — for the development of new therapeutic approaches.

Large oncosomes are vesicles released by tumor cells that have the ability to metastasize to distant sites in the body. While only a small percentage of prostate cancers produce oncosomes, experimental data from the Di Vizio team suggests that prostate cancers that produce oncosomes at the beginning of the disease have a high probability of becoming aggressive later on.

Di Vizio's study, published in Cancer Research, examined the tissue around the tumor known as the stroma, or tumor microenvironment, and in particular cells called fibroblasts. Fibroblasts are benign cells that constitute the supportive structure for the tumor. The main goal of the study was to determine if and how large oncosomes could alter the stroma. Results show that large oncosomes activate specific pathways in the stroma, and that this activation results in a more tumor-permissive function of the stroma itself.

"We now know that once a tumor arises, the cancer cells 'communicate' with the tumor microenvironment, altering it in a way that contributes to the reprogramming of normal prostate stromal cells, which in turn helps the cancer cells to grow," Di Vizio said.

"If we identify at diagnosis the cancer patients who produce large oncosomes, we will be able to treat them with more aggressive strategies," she added. "We can leave patients with less advanced disease alone, allowing them to avoid treatments such as chemotherapy that can carry unpleasant side effects."

The study addresses a major clinical issue: how to predict whether prostate cancer in a given patient will become life-threatening. Overall, more than 98 percent of prostate cancer patients survive at least five years after diagnosis, according to the National Cancer Institute. But that figure falls below 30 percent if the cancer metastasizes.

"The criteria that have been used so far to distinguish between aggressive and non-aggressive cancer are imperfect," said Valentina R. Minciacchi, PhD, the study's first author. "When men are diagnosed with prostate cancer, predictions about metastasis are not reliable."

Di Vizio said her team hopes that understanding the early history of tumors and why some cells release oncosomes — prompting the growth of tumor cells — will help them find a way to block that mechanism with drug therapy.

"We’re learning that with prostate, breast and other cancers, if the stroma can provide resistance to the tumor cells, then the tumor won’t progress," Di Vizio said.

The study collaborators include Cedars-Sinai investigators Michael Freeman, PhD, Edwin Posadas, MD, and Neil Bhowmick, PhD, and Emanuele Cocucci, MD, PhD, of the Ohio State University College of Pharmacy. For a full list of authors, please see the published study.

The IRB number for human subjects in research referenced in this article is Pro00033050.

Research reported in this publication was supported by the National Institutes of Health under award number P50 CA092131 and by funding from Avon Breast Cancer Foundation Fund 02-2013-043, the Martz Translational Breast Cancer Research Fund, Department of Defense (PC150836), the Steven Spielberg Discovery Fund in Prostate Cancer Research, and The Ohio State University Comprehensive Cancer Center (P30-CA016058) and an intramural fund (IRP46050-502339).