A convenient and effective strategy for the enrichment of tumor-initiating cell properties in prostate cancer cells

Abstract

Stem-like prostate cancer (PrCa) cells, also called PrCa stem cells (PrCSCs) or PrCa tumor-initiating cells (PrTICs), are considered to be involved in the mediation of tumor metastasis and may be responsible for the poor prognosis of PrCa patients. Currently, the methods for PrTIC sorting are mainly based on cell surface marker or side population (SP). However, the rarity of these sorted cells limits the investigation of the molecular mechanisms and therapeutic strategies targeting PrTICs. For PrTIC enrichment, we induced cancer stem cell (CSC) properties in PrCa cells by transducing three defined factors (OCT3/4, SOX2, and KLF4), followed by culture with conventional serum-containing medium. The CSC properties in the transduced cells were evaluated by proliferation, cell cycle, SP assay, drug sensitivity technology, in vivo tumorigenicity, and molecular marker analysis of PrCSCs compared with parental cells and spheroids. After culture with serum-containing medium for 8 days, the PrCa cells transduced with the three factors showed significantly enhanced CSC properties in terms of marker gene expression, sphere formation, chemoresistance to docetaxel, and tumorigenicity. The percentage of CD133/CD44 cells was ninefold higher in the transduced cell population than in the adherent PC3 cell population (2.25 ± 0.62 vs. 0.25 ± 0.12 %, respectively), and the SP increased to 1.22 ± 0.18 % in the transduced cell population, but was undetectable in the adherent population. This method can be used to obtain abundant PrTIC material and enables a complete understanding of PrTIC biology and development of novel therapeutic agents targeting PrTICs.

Concise Review: Prostate Cancer Stem Cells: Current Understanding

“…These phenotypes included expression of surface markers CD44 + /α2β1 hi /CD133 + , expression of transporter protein ATP-binding cassette sub-family G member 2 (ABCG2) that is involved in cell detoxification and the "side population" phenotype, which is defined by Hoechst dye exclusion by tumor cells [4][5][6]. Since then, a few other markers have been described for human PCSC populations (Table 1), including CD44/CD133 (7)(8)(9), aldehyde dehydrogenase (ALDH) [10], CD166 [11], CD44 + /CD24 − [12]. PCa cells expressing these markers have capacities to self-renew and to generate the heterogeneous tumor cell subpopulations.…”

Cancer Stem Cells and Prostate Cancer: A Narrative Review

“…Since 2005, several markers have been isolated for PCSCs, such as CD44/CD133, aldehyde dehydrogenase (ALDH), CD166, and CD44+/CD24−. PCa cells expressing these markers can self-renew and generate heterogeneous cell subpopulations [20,21]. Furthermore, markers such as CD151, CD160, and podocalyxin TRA-60-1 are associated with PCSCs that give birth to tumors with hierarchical organization cell organization [22].…”