Roswell Park researchers identify driver of cancer-promoting metabolic changes

Roswell Park Comprehensive Cancer Center researchers have identified a potential key player promoting cancer progression through changes in the cell environment that are conducive to metastasis. They are presenting the results of this research at the American Association for Cancer Research (AACR) Annual Meeting 2018, which continues through April 18 in Chicago, Ill.

Marc S. Ernstoff, MD, The Katherine Anne Gioia Chair of Medicine, is the senior author and Shin La Shu, PhD, a clinical researcher with the Department of Medicine, is the first author of "Human melanoma exosomes induce metabolic reprogramming in human adult dermal fibroblasts" (abstract 5087), to be presented Wednesday, April 18, from 8 a.m. to noon CDT during the "Carcinoma-Associated Fibroblasts in Tumor Progression" poster session.

Metastasis -; the spread of cancer cells from the site where cancer first appears to other, more distant organs of the body, where new tumors form and then rapidly grow -; is often the turning point in the disease process, marking a stage at which cancer becomes difficult or impossible to treat or control.

According to the "seed and soil" theory of cancer metastasis, cancer cells that spread from the primary tumor site to other areas must find or create an environment similar to the one they came from in order to survive. To examine more closely the ability of tumor cells to influence and potentially change the healthy environment of normal cells, the researchers focused on exosomes -; small fluid-filled sacs that play important roles in cell metabolism and transport as well as communication between cells.

The research team took exosomes from human melanoma cell lines and introduced them to human dermal fibroblasts, a type of skin cell. The healthy cells rapidly absorbed the tumor-derived exosomes and displayed metabolic changes conducive to tumor growth and metastasis, including acidification through increased glycolysis and decreased oxidative phosphorylation. These changes occurred within less than 24 hours, and exosomes from human melanoma cell lines could effectively "reprogram" healthy skin cells.

"The tumor microenvironment plays a critical role in tumor metastasis, and we show -; for the first time -; that melanoma-derived exosomes can reprogram the metabolism of healthy skin cells, creating a microenvironment that is conducive to cancer progression and metastasis," says Dr. Ernstoff.

To conduct this research, the team developed an immuno-biochip that first captures exosomes and then searches them for microRNAs -; tiny molecules that influence how genes are expressed. Using this immuno-biochip, the researchers detected the microRNAs miR-155 and miR-210, both of which are known to promote the cancer-promoting metabolic changes observed.

"Our findings identify new therapeutic opportunities to study both exosomes and exosomal microRNAs as targets of interventions that reduce the likelihood of metastasis in cancer patients," adds Dr. Shu.

More than 20 teams from Roswell Park Comprehensive Cancer Center have been invited to present their research at AACR 2018. In addition, Dr. Ernstoff led the roundtable discussion "Practicing immunotherapy in the clinic" on April 14 and Kunle Odunsi, MD, PhD, FRCOG, FACOG, Deputy Director, Chair of Gynecologic Oncology and Executive Director of the Center for Immunotherapy, was lead discussant for the session "Multimodality Immuno-oncology Approaches" on April 15. Dr. Odunsi will also be the featured presenter at an April 18 Meet the Experts session, "Reprogramming the Tumor Microenvironment to Enhance 'Next-Generation' Adoptive Cellular Therapy."​

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