Scientists at have shown that EGFR may be shut down with the help of a cytokine known as MIF (macrophage migration inhibitory factor). Itâs 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, are published in the Aug. 17, 2015 issue of .
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. Itâs increasingly being recognized as a key factor in disease progression.
MIF appears to be vital to regulation of EGFR activation in tumor cellsâ extracellular or external environment.
âMIF can be secreted from both tumor and immune cells,â said , professor of . âImportantly, secreted MIF is modified by an attached sugar group which allows MIF to gain a specific new function compared to its non-modified form.â
Luâs 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.
âCancer cells secret MMP13, an enzyme involved in many phases of cancer progression,â said Lu. âMMP13 degrades extracellular MIF impacting EGFR in such a way that it promotes EGFR activation, tumor cell invasion, and finally, forms brain tumors.â
The teamâs findings demonstrate an important mechanism underlying amplified EGFR activation in tumors. This is mediated by downregulation of its antagonist, MIF, in the tumor microenvironment.
Lu said that understanding the synergies between EGFR and MIF provide an âinstrumental insightâ into tumor progression and could open up new approaches to treating cancer by intervening in this self-regulating loop.
MD Anderson team members included Yanhua Zheng, Ph.D., Xinjian Li, Ph.D., Xu Qian, Ph.D., Yugang Wang, Ph.D., Jong-Ho Lee, Ph.D., and Yan Xia, Ph.D., all of Neuro-Oncology; and David Hawke, Ph.D., Systems Biology.
Other participating institutions were the Affiliated Hospital of Hebei University, Baoding, China; and Wenzhou Medical University, Wenzhou, China.
The study was funded by the National Cancer Institute (2R01 CA109035, 1R01 CA 169603), the National Institute of Neurological Disorders and Stroke (1R01 NS089754), the National Institutes of Health (CA016672, 1S10 OD012304-01, and the MD Anderson Brain Cancer SPORE grant CA127001); the James S. McDonnell Foundation 21st Century Science Initiative in Brain Cancer Research Award; and the Cancer Prevention and Research Institute of Texas (RP130397).
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