MERIT Award Recipient: Mary J. Hendrix, Ph.D.
Endothelial Transdifferentiation of Invasive Tumor Cells
One of the hallmarks of aggressive cancer cells is their unspecialized nature, which is similar to that of embryonic stem cells. The biological events underlying the change from normal, specialized melanocyte to unspecialized melanoma cell is not well understood. The Hendrix laboratory has hypothesized that the unspecialized or poorly differentiated phenotype serves as an advantage to cancer cells by enhancing their ability to migrate, invade and metastasize virtually undetected by the immune system.
To test this hypothesis, Dr. Hendrix and coworkers collaborated with the National Human Genome Research Institute to define the molecules or proteins present in patient-derived aggressive melanoma cells but absent in poorly aggressive melanoma cells. The results supported the premise that aggressive melanoma cells contained proteins similar to those of an embryonic stem cell. These studies led to the first molecular classification of malignant melanoma and to the discovery that aggressive melanoma cells can mimic other cell types, such as those that normally form blood vessels.
The discovery that melanoma cells can look similar to vascular cells also may help explain how melanoma cells evade immune detection. Based on these findings, the new concept of "vasculogenic mimicry" was introduced to describe the ability of aggressive melanoma cells to express molecules associated with vascular cells and to form embryonic-like vasculogenic networks that may help to supply blood to tumors. Other integral studies have led to the discovery that melanoma cells can produce specific molecules that are released into the cells' microenvironments and further modified into fragments that stimulate the melanoma cells to migrate. These findings will be realized in the provision of new molecular markers for clinical diagnosis of aggressive melanoma tumor cells, and novel molecular targets for therapeutic intervention strategies.