Researchers from Children's Memorial Research Center, Northwestern University have found a new model that shows how tumor cells interacts with the surrounding normal skin cells in the presence of microenvironment of tumor cells. The process of metastasis spread and transformation from normal skin cell to malignant cell is understood with the help of this new model.
"Our findings offer new insights into the influence of the tumor cell microenvironment on the transformation of normal skin cells, as well as on genetic triggering mechanisms and signaling pathways that could be targeted for novel therapeutic strategies to inhibit the spread of melanoma," Hendrix said.
Metastatic cancer cells are characterized by increased tumor cell invasion and migration, as well as an undifferentiated, or "plastic," nature.
The Hendrix lab has hypothesized that this poorly differentiated cell type serves as an advantage to aggressive cancer cells by enhancing their ability to metastasize virtually undetected by the immune system. The group's current study tested the hypothesis that the microenvironment of metastatic melanoma cells could induce benign skin cells to become cancer-like.
The researchers seeded a particularly aggressive form of human metastatic melanoma cells onto a three-dimensional collagen matrix and allowed the cells to precondition the microenvironment for several days. The malignant melanoma cells were removed and the matrix was left intact.
Then, normal human skin cells were seeded onto the melanoma-preconditioned matrix and were allowed to remain for several days.
After this period, the previously normal cells seeded onto the matrix preconditioned by the metastatic melanoma were reprogrammed to express genes (produce specific gene proteins) associated with a highly plastic cell type similar to the aggressive melanoma cells used in the study.
Removal of the "transdifferentiated" skin cells from the melanoma microenvironment caused the cells to revert to their original appearance.
"There were no significant genetic changes between normal skin cells grown on an untreated matrix and those exposed to a matrix preconditioned by human metastatic melanoma cells, further supporting the hypothesis that "epigenetic" induction of changes in skin cell gene expression is directly related to exposure to the metastatic microenvironment," the authors said.