How To Capture Quickly Cancer Markers

A nanoscale product of human cells that was once considered junk is now known to play an important role in intercellular communication and in many disease processes, including cancer metastasis. Researchers at Penn State have developed nanoprobes to rapidly isolate these rare markers, called extracellular vesicles (EVs), for potential development of precision cancer diagnoses and personalized anticancer treatments.

Lipid nanoprobes

Most cells generate and secrete extracellular vesicles,” says Siyang Zheng, associate professor of biomedical engineering and electrical engineering. “But they are difficult for us to study. They are sub-micrometer particles, so we really need an electron microscope to see them. There are many technical challenges in the isolation of nanoscale EVs that we are trying to overcome for point-of-care cancer diagnostics.”

At one time, researchers believed that EVs were little more than garbage bags that were tossed out by cells. More recently, they have come to understand that these tiny fat-enclosed sacks — lipids — contain double-stranded DNA, RNA and proteins that are responsible for communicating between cells and can carry markers for their origin cells, including tumor cells. In the case of cancer, at least one function for EVs is to prepare distant tissue for metastasis.

The team’s initial challenge was to develop a method to isolate and purify EVs in blood samples that contain multiple other components. The use of liquid biopsy, or blood testing, for cancer diagnosis is a recent development that offers benefits over traditional biopsy, which requires removing a tumor or sticking a needle into a tumor to extract cancer cells. For lung cancer or brain cancers, such invasive techniques are difficult, expensive and can be painful.

Noninvasive techniques such as liquid biopsy are preferable for not only detection and discovery, but also for monitoring treatment,” explains Chandra Belani, professor of medicine and deputy director of the Cancer Institute,Penn State College of Medicine, and clinical collaborator on the study.

We invented a system of two micro/nano materials,” adds Zheng. “One is a labeling probe with two lipid tails that spontaneously insert into the lipid surface of the extracellular vesicle. At the other end of the probe we have a biotin molecule that will be recognized by an avidin molecule we have attached to a magnetic bead.”


How Cancer Cells Invade The Body

Using a nanocomputer that acts as an obstacle course for cells, researchers from the Brown School of Engineering have shed new light on a cellular metamorphosis thought to play a role in tumor cell invasion throughout the body.

The epithelial-mesenchymal transition (EMT) is a process in which epithelial cells, which tend to stick together within a tissue, change into mesenchymal cells, which can disperse and migrate individually. EMT is a beneficial process in developing embryos, allowing cells to travel throughout the embryo and establish specialized tissues. But recently it has been suggested that EMT might also play a role in cancer metastasis, allowing cancer cells to escape from tumor masses and colonize distant organs.

For this study, published in the journal Nature Materials, the researchers were able to image cancer cells that had undergone EMT as they migrated across a device that mimics the tissue surrounding a tumor.
emt pillarsBenign cancer cells that had been induced to become malignant made their way slowly around microscopic obstacles. About 16 percent of the cells moved much more rapidly across the microchip
People are really interested in how EMT works and how it might be associated with tumor spread, but nobody has been able to see how it happens,” said lead author Ian Wong, assistant professor in the Brown School of Engineering and the Center for Biomedical Engineering, who performed the research as a postdoctoral fellow at Massachusetts General Hospital. “We’ve been able to image these cells in a biomimetic system and carefully measure how they move.”