MCI Researchers Explore Role of Tiny Messengers in Cancer

MOBILE, Alabama – Think of exosomes as tiny mail carriers. These small membrane sacs, released by all cells and found in all body fluids, are the focus of increasing research. Scientists hope to one day exploit exosomes for early disease diagnosis, prognosis, therapy and to expand their role in efficient drug delivery.

Researchers at USA Health Mitchell Cancer Institute are investigating exosomes’ multifaceted roles in cancer and their use as data-rich resources for discovering biomarkers for cancer.

The research laboratory of Dr. Ajay Singh, Ph.D., who studies the cross-talk of tumor cells with other cells in the body, is investigating exosomes for their role in the adaptive response of tumor cells to changing environmental conditions. During their growth, tumor cells are subjected to extremely harsh conditions, such as the limited availability of oxygen and nutrients. Despite this, tumor cells not only survive but also emerge as a highly aggressive disease. “We believe that exosomes play a major role in these adaptive responses,” Dr. Singh said.

Worldwide, scientists have only begun to explore the role of exosomes over the past decade. In 2007, Swedish scientist Jan Lotvall of the University of Gothenburg showed that some cells use exosomes to transfer genetic material such as messenger RNAs to make proteins and microRNAs to regulate the expression of genes. Lotvall’s work was published in Nature Cell Biology, and interest took off.

At the Mitchell Cancer Institute, graduate student Mary Patton, a member of the Singh lab team, has found that under low-oxygen conditions, pancreatic tumor cells secrete more exosomes carrying different biomaterial, which when transferred to other tumor cells enable them to survive better and become more aggressive. She will present her findings at the annual meeting of the American Association of Cancer Research to be held in Atlanta this spring.

In a recently published article in the British Journal of Cancer, Dr. Singh’s team demonstrated a role that exosomes play in the acquired chemoresistance of pancreatic cancer. In collaboration with MCI physician-scientist Dr. Moh’d Khushman, the group is expanding this research to patients to examine the potential of exosomes in monitoring the response to chemotherapy. The team is also collaborating with MCI researcher Dr. Seema Singh to explore the use of exosomes as efficient and tumor-targeted drug deliverers.

Steve McClellan, who has studied exosomes for the past two years as chief of MCI’s Flow Cytometry Lab, has been working to develop a sensitive procedure to detect and characterize exosomes based on their surface marker composition. He has been collaborating with Drs. Singh and Khushman to develop an exosome-based blood test to detect pancreatic cancer early and to enable the monitoring of patients’ response to chemotherapy.

McClellan’s webinar on using Flow Cytometry to analyze exosomes on behalf of biotech company ThermoFisher was viewed by thousands of scientists worldwide.

“It is my belief that these tiny particles will unlock the greatest advances in medicine in the next 20 years,” he said.