Researchers have discovered that activating growth factor receptors such as epidermal growth factor receptors (EGFR) cause tumor progression in several types of cancer. University of Texas MD Anderson Cancer Center‘s Scientists have demonstrated that EGFR might be turned off thanks to a cytokine also known as MIF (macrophage migration inhibitory factor). The research team strongly believes that this finding can transform the way medicine is treating tumors.
Research has not yet identified the precise mechanism through which EGFR activation is regulated within the tumor micro-environment or whether human cells’ own external antagonists are capable of regulating EGFR. When investigating the tumor micro-environment, researchers tend to focus on the cellular landscape in which the tumor is located, which includes the immune cells, surrounding blood vessels, fibroblasts and further structures and cells. This approach is being increasingly recognized as the key factor to understand disease progression.
MIF seems to be vital in the regulation of the EGFR activation in tumor cells’ external environment. “MIF can be secreted from both tumor and immune cells,” explained Zhimin Lu, who is a professor of Neuro-Oncology. “Importantly, secreted MIF is modified by an attached sugar group which allows MIF to gain a specific new function compared to its non-modified form.”
Lu and his team found that the modified MIF has the capacity to bind itself to EGFR, which inhibits it (the EGFR) because it blocks the epidermal growth factor to bind to the EGFR in cancer cells.
“Cancer cells secret MMP13, an enzyme involved in many phases of cancer progression. MMP13 degrades extracellular MIF impacting EGFR in such a way that it promotes EGFR activation, tumor cell invasion, and finally, forms brain tumors,” noted Lu.
These findings reveal the amplified EGFR activation mechanism in tumors, which is mediated by the down regulation of MIF, its antagonist. The interaction and synergy of MIF and EGFR are an accurate tool to assess tumor progression and might offer new approaches of treating cancer in the future.