Scientists Find Way to Make Cancerous and Healthy Cells Thrive in the Lab

In a major step that could transform biomedical research, scientists have found a way to keep tumor cells as well as healthy cells taken from a cancer patient alive in the laboratory, which previously had not been possible. Normal cells typically die in the lab after dividing only a few times, and many common cancers will not grow, unchanged, outside of the body.

This new technique, reported online December 19, 2011, in the American Journal of Pathology, could be the key development that drives in a new era of customized cancer medicine, and has potential application in regenerative medicine, according to the study’s lead investigator, Richard Schlegel, MD, PhD, chairman of the department of pathology at Georgetown Lombardi Comprehensive Cancer Center (Washington DC, USA), a part of Georgetown University Medical Center. “Because every tumor is unique, this advance will make it possible for an oncologist to find the right therapies that both kills a patient’s cancer and spares normal cells from toxicity,” he said. “We can test resistance as well chemosensitivity to single or combination therapies directly on the cancer cell itself.”

The researchers, which also include several scientists from the US National Institutes of Health (NIH; Bethesda, MD, USA), revealed that by adding two different substances to cancer and normal cells in a laboratory forces them to change into stem-like cells--adult cells from which other cells are produced.

The two substances are a Rho kinase (ROCK) inhibitor and fibroblast feeder cells. ROCK inhibitors help block cell movement, but it is unclear why this agent turns on stem cell attributes, Schlegel says. His coinvestigator Alison McBride, PhD, of the National Institute of Allergy and Infectious Diseases (Bethesda, MD, USA), had discovered that a ROCK inhibitor allowed skin cells (keratinocytes) to reproduce in the laboratory while feeder cells kept them alive.

The Georgetown researchers--13 investigators in the departments of pathology and oncology-- tried ROCK inhibitors and fibroblast feeder cells on the nonkeratinocyte epithelial cells that line glands and organs to see if they had any effect. They found that both were needed to produce a dramatic effect in which the cells visibly changed their shape as they reverted to a stem-like state.

“We tried breast cells and they grew well. We tried prostate cells and their growth was fantastic, which is amazing because it is normally impossible to grow these cells in the lab,” Dr. Schlegel stated. “We found the same thing with lung and colon cells that have always been difficult to grow. In short, we discovered we can grow normal and tumor cells from the same patient forever, and nobody has been able to do that,” he said. “Normal cell cultures for most organ systems can’t be established in the lab, so it wasn't possible previously to compare normal and tumor cells directly.”

The ability to immortalize cancer cells will also make biobanking both viable and relevant, according to Dr. Schlegel. The researchers further discovered that the stem-like behavior in these cells is reversible. Removing the ROCK inhibitor forces the cells to differentiate into the adult cells that they were initially. This “conditional immortalization” could help further the field of regenerative medicine, noted Dr. Schlegel.

However, the most direct change in medical practice from these findings is the potential they have in “revolutionizing what pathology departments do,” Dr. Schlegel said. “Today, pathologists don’t work with living tissue. They make a diagnosis from biopsies that are either frozen or fixed and embedded in wax. In the future, pathologists will be able to establish live cultures of normal and cancerous cells from patients, and use this to diagnose tumors and screen treatments. That has fantastic potential.”

Georgetown University and the National Institutes of Health have filed two patent applications on technologies described in this paper.

Related Links:
Georgetown University Lombardi Comprehensive Cancer Center
US National Institutes of Health