Long-overlooked “tunneling nanotubes” and other bridges between cells act as conduits for sharing RNA, proteins or even whole organelles.
Breast cancer cells in culture form tubelike interconnections. Such connections may help cancer cells share their resistance to therapeutic drugs. When the physician and scientist Emil Lou was an oncology fellow at Memorial Sloan Kettering Cancer Center about a decade ago, he was regularly troubled by the sight of something small but unidentifiable in his cancer-cell cultures. Looking through the microscope, he said, he “kept finding these long, thin translucent lines,” about 50 nanometers wide and 150 to 200 microns long, extending between cells in the culture. He called on the world-class cell biologists in his building to explain these observations, but nobody was sure what they were looking at.
Finally, after delving into the literature, Lou realized that the lines matched what Hans Hermann Gerdes’’ group at the University of Heidelberg had described as “nanotubular highways” or “tunneling nanotubes” (TNTs) in Science. Lou worried that the lines he’d noticed might be illusory, so he checked the archive of tumor specimens from patients at the cancer center. Lo and behold, the same long cellular processes were present in the tumors, too, so he set out to investigate their relevance. Since then, as a faculty member at the University of Minnesota, he’s found evidence that tumor cells use these TNTs to share molecular messages in the form of short regulatory snippets of RNA called microRNA, enabling cancer cells resistant to chemotherapy drugs to confer the same resistance on their neighbors.
How did the tunneling nanotubes go unnoticed for such a long time?
Lou notes that in the last couple of decades, cancer research has centered primarily on detecting and therapeuticallytargeting mutations in cancer cells — and not the structures between them. “It’s right in front of our face, but if that’s not what people are focusing on, they’re going to miss it,” he said. That’s changing now. In the last few years, the number of researchers working on TNTs and figuring out what they do has risen steeply. Research teams have discovered that TNTs transfer all kinds of cargo beyond microRNAs, including messenger RNAs, proteins, viruses and even whole organelles, such as lysosomes and mitochondria.
“It’s only the tip of the iceberg,” Lou said. “It’s a pretty exciting time to look at these.”
These fragile structures are appearing not only in the context of conditions such as cancer, AIDS and neurodegenerative diseases, but also in normal embryonic development. Healthy adult cells don’t usually make TNTs, but stressed or ailing cells appear to induce them by sending out signals to call for help. It’s unclear, though, how healthy cells sense that their neighbors need help or how they physiologically “know” what specific cargo to send.
Source: Quanta Magazine