Scientists from the University of North Carolina at Charlotte, North Carolina Central University’s Nutrition Research Program at the NC Research Campus in Kannapolis, NC, and the Carolinas Medical Center in Charlotte, NC have teamed up to identify molecular targets in the signaling pathway for pancreatic ductal adenocarcinoma (PDA) tumors. Their study was published in the journal Oncogene last month.
By investigating the key molecular players in the signaling pathway that leads to pancreatic ductal adenocarcinoma (PDA) tumor growth, these researchers may have found a way to block communication to reduce cancer growth.
Mucin1 (MUC1) is a transmembrane glycoprotein that, in addition to intracellular signaling, is involved in developing protective mucous barriers on epithelial surfaces. MUC1 is overexpressed in more than 80 percent of PDA cases, which lead the team of researchers to look further at the role of MUC1 in tumor growth.
MUC1 creates a pro-angiogenic tumor microenvironment, forming a network of blood vessels for the abnormally growing tissues to access. MUC1 does so by activating neuropilin-1 (NRP1), also a transmembrane protein and a co-receptor of vascular endothelial growth factor (VEGF) and its ligand.
PDA cells with high levels of tumor-associated MUC1 (tMUC1) and subsequently high levels of NRP1 induce cancer-friendly conditions through signaling with VEGF with a few different actions that as observed in this study, include:
- Induction of endothelial cell tube formation.
- Generation of abnormally positioned blood vessels.
- Enhancement of distant metastasis (as observed in a zebrafish xenograft model).
The relationship between MUC1, NRP1, and VEGF produces an “attractive therapeutic target” for suppressing PDA tumors, and the UNC Charlotte, NC Central, and Carolinas Medical Center researchers uniquely demonstrated that tMUC1 does indeed prompt high levels of NRP1 that lead to a pro-angiogenic tumor microenvironment that does not exist in PDA tumors with low to zero levels of tMUC1. Inhibiting signaling between NRP1 and VEGF suppresses tumor growth, as the team saw in mice models of disease. They did so with an NRP1 antagonist that inhibits the communication between VEGF and NRP1, to cut off all pro-tumor reactions that lead to more lethal cancer growth.
To see the entire journal article, click here.
By Kara Marker, NCRC Marketing Intern