Accumulating evidence suggests that a subset of cancer cells, operationally termed cancer stem cells (CSCs) or tumor-initiating cells, possesses enhanced ability to generate tumors. Cancer stem cells are implicated in tumor progression and metastasis, although the exact mechanisms remain poorly understood. Professor Quan Chen’s lab reported that cellular prion protein (PrPc, PRNP), co-expressing with CD44, identifies a functionally distinct subpopulation of CD44⁺ CCSCs, which contributes to CRC initiation and metastasis.

PrPc is a highly-conserved glycoprotein present in all vertebrates and has the same protein sequence as the scrapie prion protein (PrPsc), a pathogenic factor in scrapie in sheep，bovine spongiform encephalopathy in cattle, and kuru in human beings. Professor Quan Chen’s lab purified PrPc⁺ and PrPc^- CD44-positive cancer stem cells from patient tumors and injected these cells into the cecal wall of NOD/SCID mice. Remarkably, liver metastases were exclusively observed in the mice implanted with PrPc⁺ but not PrPc^- cancer stem cells. Further investigation revealed that PrPc promoted epithelial to mesenchymal transition (EMT) via the ERK2 (MAPK1) pathway, thereby conferring high metastatic capacity. Tissue microarray analysis also confirmed that PrPc expression level is positively correlated with an increased risk of metastasis in colorectal cancer. Notably, administration of PrPc monoclonal antibodies significantly inhibited tumorigenicity and metastasis of colorectal cancer stem cells in orthotopic mouse models.

This work was supported by initiative of stem cell and regenerative medicine from Chinese Academy of Sciences (XDA01040409), the 973 project from the Ministry of Science and Technology (MOST) of China (2009CB512800 and 2010CB912204), grant from the National Natural Science Foundation of China (NSFC) (81130045 and 31000614). This work was published in Cancer Research：

http://cancerres.aacrjournals.org/content/early/2013/02/14/0008-5472.CAN-12-3759.full.pdf+html