Targeting the normal cells that surround cancer cells within and around a tumor is a strategy that could greatly increase the effectiveness of traditional anti-cancer treatments, say researchers at The Wistar Institute.
In the Journal of Clinical Investigation published online November 16, they demonstrate the critical role for fibroblast activation protein (FAP), expressed by one type of these so-called "stromal" cells, in promoting tumor growth in mice. Genetically deleting or therapeutically targeting FAP significantly reduced the rate of tumor growth in mice by interrupting or blocking important signaling pathways and biological processes required for tumor growth, the Wistar team found.
"It's like taking away the soil from a seed that wants to grow," says senior author Ellen Pur, Ph.D., a professor in the Molecular and Cellular Oncogenesis Program at Wistar. "These results provide a proof-of-principle that targeting and modifying a tumor's microenvironment may be an effective approach to treating solid tumors."
Tumors are a complex mix of neoplastic cancer cells and normal cells inflammatory and immune cells, endothelial cells, fibroblasts, pericytes, and others, collectively known as stromal cells. In addition, a web-like extracellular matrix is created by the stromal cells, and its structure is important for supporting and nurturing tumor growth through molecular signaling pathways.
The Wistar team focused on fibroblasts and pericytes. In addition to synthesizing components of the extracellular matrix, fibroblasts associated with tumors also express FAP, a particular protease that cuts up other proteins while pericytes are important to the function of the new blood vessels that develop in tumors. FAP is expressed in 90 percent of all human epithelial (solid) cancers, and FAP expression is recognized as a marker for and is thought to play a role in cancer growth, but the mechanisms through which this occurs had
|Contact: Staci Vernick Goldberg|
The Wistar Institute