Scientists know that activation of growth factor receptors such as epidermal growth factor receptors (EGFR) promote tumor progression in many types of cancer.
MD Anderson scientists have shown that EGFR may be shut down with the help of a cytokine known as MIF (macrophage migration inhibitory factor). It’s a finding they believe could signal a new way to look at treating tumors.
Their study results, which focused on brain, breast, and prostate cancer, were published last month in Nature Cell Biology.
Exactly how EGFR activation is regulated in the tumor microenvironment has not been understood, nor do human cells have an external antagonist that regulates EGFR. The tumor microenvironment is the cellular landscape in which a tumor exists, including surrounding blood vessels, immune cells, fibroblasts and other cells and structures. It’s increasingly being recognized as a key factor in disease progression.
MIF appears to be vital to regulation of EGFR activation in tumor cells’ extracellular or external environment.
“MIF can be secreted from both tumor and immune cells,” said Zhimin Lu, M.D., Ph.D., professor of Neuro-Oncology. “Importantly, secreted MIF is modified by an attached sugar group that allows MIF to gain a specific new function compared to its non-modified form.”
Lu’s team discovered that the modified MIF binds to EGFR. This inhibits EGFR by blocking the epidermal growth factor to bind to EGFR in cancer cells.
The team’s findings demonstrate an important mechanism underlying amplified EGFR activation in tumors. This is mediated by downregulation of its antagonist, MIF, in the tumor microenvironment.
Read more about this discovery in the Newsroom section of MD Anderson’s website.