Identification of CD166 as a Surface Marker for Enriching Prostate Stem/Progenitor and Cancer Initiating Cells

Abstract

New therapies for late stage and castration resistant prostate cancer (CRPC) depend on defining unique properties and pathways of cell sub-populations capable of sustaining the net growth of the cancer. One of the best enrichment schemes for isolating the putative stem/progenitor cell from the murine prostate gland is Lin-;Sca1+;CD49fhi (LSChi), which results in a more than 10-fold enrichment for in vitro sphere-forming activity. We have shown previously that the LSChi subpopulation is both necessary and sufficient for cancer initiation in the Pten-null prostate cancer model. To further improve this enrichment scheme, we searched for cell surface molecules upregulated upon castration of murine prostate and identified CD166 as a candidate gene. CD166 encodes a cell surface molecule that can further enrich sphere-forming activity of WT LSChi and Pten null LSChi. Importantly, CD166 could enrich sphere-forming ability of benign primary human prostate cells in vitro and induce the formation of tubule-like structures in vivo. CD166 expression is upregulated in human prostate cancers, especially CRPC samples. Although genetic deletion of murine CD166 in the Pten null prostate cancer model does not interfere with sphere formation or block prostate cancer progression and CRPC development, the presence of CD166 on prostate stem/progenitors and castration resistant sub-populations suggest that it is a cell surface molecule with the potential for targeted delivery of human prostate cancer therapeutics.

Expression and significance of S100P, CD147, and OCT4 in different prostate cancer tissue TNM stages

“…Previous studies showed that androgen receptor expression in cells overexpressing S100P increased significantly, and that there is a close relationship between androgen receptors and cell proliferation (Lee et al, 2011). Accordingly, Jiao et al (2012) found that S100P expression promoted prostate cancer progression both in vitro and in vivo. Our study showed that the S100P expression positive rate in patients with distant metastasis was 4.00%, significantly lower than that of patients without metastasis.…”

“…It has a very important role in maintaining the self-renewal and pluripotency ability of embryonic stem cells. Several studies have found that OCT4 expression in the healthy population is low, whereas OCT4 expression is high in gallbladder carcinoma, pancreatic cancer, and liver cancer (Wang et al, 2012). Specially, its expression level is upregulated following clinical upstaging.…”

New insights into prostate cancer stem cells

“…Although castration-resistant PCSCs have not yet been uncovered in primary human PCa samples, recent studies have provided hints that some PCSC subpopulations may express low levels of AR and intrinsically be resistant to castration. 8,11,55,99 It is conceivable that the expansion of such cells may promote CRPC development. As a result, these castration-resistant PCa cells may represent potential cellular targets for novel drug development.…”

“…53 Moreover, cancer cells expressing a luminal phenotype can regenerate new tumors after androgen replacement, 53 suggesting that SC-like cancer cells with the luminal progenitor phenotypes might be candidate cells of origin for CRPC. A cell surface marker, CD166, is found to be highly expressed in human CRPC samples, and, importantly, LSC hi CD166 hi cells in the Pten-null model have much enhanced sphere-formation abilities compared with the other subpopulations, 55 suggesting that the CD166 hi cell population may be enriched in castrationresistant PCSCs. Work from our lab indicates that PSA −/lo PCa cells are more clonal and clonogenic than the corresponding bulk PSA + PCa cells in androgen-deficient conditions in vitro and are more tumorigenic than PSA + cells in fully castrated mice.…”

The role of novel and known extracellular matrix and adhesion molecules in the homeostatic and regenerative bone marrow microenvironment

“…218,219 In various tumors, cancer stem cells can be identified by high membrane expression of CD166. 220,221 These studies show that CD166 regulates self-renewal in HSCs and tumor cells, and its expression in the endosteal niche and HSPCs is essential for proper hematopoiesis.…”