Taming Cancer: Researchers Transform Melanoma back to Normal Tissue

The key to cancer, and the key to aging, is learning how to control the differentiation and de-differentiation of cells. A previous article here discusses the same general topic.

Scientists at Northwestern University and the Stowers Institute for Medical Research have reprogrammed malignant melanoma cells to become normal melanocytes, or pigment cells, a development that may hold promise in treating of one of the deadliest forms of cancer.

A report describing the group's research was published in the Feb. 27 online edition of the Proceedings of the National Academy of Sciences that will appear in the March 7 issue of the journal.

The experiments were conducted as a collaboration involving the laboratories of Mary J. C. Hendrix, president and scientific director of the Children's Memorial Research Center, Northwestern University Feinberg School of Medicine, and Paul M. Kulesa, director of Imaging at the Stowers Institute for Medical Research in Kansas City, Mo.

The study demonstrated the ability of malignant melanoma cells to respond to embryonic environmental cues in a chick model -- in a manner similar to neural crest cells, the cell type from which melanocytes originate -- inducing malignant cells express genes associated with a normal melanocyte.

The researchers also showed that the malignant melanoma cells lost their tumor-causing ability as they became reprogrammed by the embryonic microenvironment to assume a more normal melanocyte-like cell type.

"Using this innovative approach, further investigation of the cellular and molecular interactions within the tumor cell embryonic chick microenviroment should allow us to identify and test potential candidate molecules to control and reprogram metastatic melanoma cells," Hendrix said.

....Kulesa's laboratory transplanted adult human metastatic melanoma cells, isolated and characterized by the Hendrix laboratory group, into the neural tube of chick embryos.

The transplanted melanoma cells did not form tumors.

Rather, like neural crest cells, the melanoma cells invaded surrounding chick tissues in a programmed manner, distributing along the neural-crest-cell migratory pathways throughout the chick embryo.

The investigators found that a subpopulation of the invading melanoma cells produced markers indicative of skin cells and neurons that had not been present at the time of transplantation.

Taken together, results of this study suggest that human metastatic melanoma cells respond to and are influenced by the chick embryonic neural-crest-rich microenvironment, which may hold promise for the development of new therapeutic strategies, the researchers said.

"This idea was pioneered 30 years ago by scientists who thought that the complex signals within an embryonic field may reprogram an adult metastatic cancer cell introduced into such an environment and cause it to contribute in a positive way to an embryonic structure," Kulesa said.

....One of the hallmarks of aggressive cancer cells, including malignant melanoma, is their unspecified, plastic nature, which is similar to that of embryonic stem cells.

The Hendrix lab has shown that the unspecified or poorly differentiated cell type serves as an advantage to cancer cells by enhancing their ability to migrate, invade and metastasize virtually undetected by the immune system.

Read the entire report here.

Whether a cell becomes one tissue type, another tissue type, a stem cell, or a cancer cell--is determined by the gene expression of that cell. Scientists are closing in on the signals that control a cell's gene expression.