The colorectal cancer is the fourth most common type of cancer in the world. The search for potential molecular targets for therapy has led to the Cellular Prion Protein (PrPC) as a possible candidate. Its activity depends on the interaction with the secreted form of the stress inducible protein 1 or heat shock organizing protein (STI1/HOP). Previous results indicated the importance of the PrPC-STI1/HOP complex in proliferation of glioblastomas and invasion of melanomas. Therefore, this work aims to understand how PrPC-STI1/HOP complex can influence the migration and invasion of WiDr and HCT8 colorectal tumor cells. PrPC is equally expressed at the cell surface of both cell lines. Cell migration assays were performed using boyden chambers and recombinant STI1/HOP as chemical attractant. For invasion experiments cells were seeded on boyden chambers covered with matrigel and treated with STI1/HOP. The results showed that when stimulated with recombinant STI1/HOP, both tumor cell lines showed higher migration and invasion potentials than non-treated cells or those treated with a STI1/HOP deletion mutant for the PrPC binding domain (STI1Δ230-245). Moreover, migration and invasion mediated by PrPC-STI1/HOP complex were blocked by a STI-1/HOP (230-245) peptide, which mimics STI1 binding site to PrPC or also by a neutralizing anti-PrPC antibody. STI1/HOP is secreted in the conditioned medium (CM) within extracellular microvesicles (MVs) and WiDr cells secreted more MVs and STI1/HOP than HCT8 cells. Remarkable, HCT8 cells treated with CM or isolated MVs from WiDr cells show a higher migration than that induced when the former cells were treated with their own CM or when WiDr cells were treated with CM or MVs derived from HCT8 cells. Together, these results indicate that the PrPC-STI1/HOP complex mediate migration and invasion of colorectal tumor cells and suggest that cellular migration is dependent on the concentration of secreted MVs. The role of STI1/HOP present in MVs on cell migration is still under investigation.
Citation Format: Tonielli S. Lacerda, Marcos Vinicios S. Dias, Antuani Rafael Baptistella, Fernanda S. Giudice, Bruna R. Roz, Iara S. Rodrigues, Vilma Regina Martins. Prion protein and its ligand STI1/HOP modulate migration and invasion of cell lines derived from colorectal tumors. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4051. doi:10.1158/1538-7445.AM2014-4051