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New findings in cell communication may contribute to new cancer treatments

Image courtesy of Dr. Emil Lou

Human ovarian cancer SKOV3 OC cells (stained green) connected with immortalized ovarian surface epithelial cell stromal cells (stained red) via tunneling nanotubes.

Researchers from the University of Minnesota recently discovered cells directly transfer tumor-causing microRNAs via tunneling nanotubes, or long cellular extensions of cancer cells facilitating intercellular communication. Intercellular communication is vital to survival in multicellular organisms. Communication between distant and proximal cells is especially important to cancerous tumor growth.

In this study, the authors demonstrated for the first time that genetic materials known as microRNAs can travel directly between cancer cells, and even from cancers to normal cells, via these nanotube pipelines.

This article is featured in the November issue of Translational Research, which named senior author Emil Lou, M.D., Ph.D., the Featured New Investigator for the month.

Lou, a gastrointestinal oncologist and assistant professor in the University of Minnesota Medical School, collaborated on the study with Subree Subramanian, Ph.D., assistant professor in the Department of Surgery, and Clifford Steer, M.D., professor of medicine. Other authors include Venugopal Thayanithy, Ph.D., research associate in the Lou Lab, and Elizabeth Dickson, surgical fellow in Gynecologic Oncology. All collaborators are members of the Masonic Cancer Center, University of Minnesota.

“Our previous research showed nanotubes have potential relevance to cancer communication and spread,” said Lou. “This next step was to determine whether microRNAs could also transfer from cell to cell, as the implications could help explain how these gene-altering signals are amplified in many forms of cancers.”

MicroRNAs are important in this discovery because once microRNA is transferred from a very aggressive cancer cell to a less aggressive cancer cell, it may cause that cell to become more aggressive, ultimately increasing the ability of the cancer to grow and spread.

“Abnormal changes in microRNA levels can affect normal cell function” said Subramanian. “Direct transfer of microRNAs from aggressive cancer cells to normal cells via tunneling nanotubes can affect many cellular functions in the recipient cells”.

“We utilized new methodologies to detect the nanotubes in malignant ovarian tumors from human patients as well as osteosarcoma from mice,” said Thayanithy. “By tagging the microRNAs with altered expressions, we were able to see how they move between cells using the nanotubes. Surprisingly, the microRNAs transferred commonly from cancer to non-cancer cells for both sarcoma and ovarian cancers, showing the potential effects that cancer cells have for altering the surrounding cells in tumors. We are continuing to study what impact the microRNAs have once they make it to their target cells.”

Researchers in the Lou lab will utilize this discovery to better understand the function of these nanotubes and the best way to cut the lines of communication. The overall goal will be developing strategies to translate into therapy to treat cancers by stopping these types of cell communication.


Tumor-stromal cross talk: direct cell-to-cell transfer of oncogenic microRNAs via tunneling nanotubes

Tunneling nanotubes: novel potentials for old players

Lou lab

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