Advances in surface markers of liver cancer stem cell

Abstract

Liver cancer stem cells (LCSCs), a small subpopulation that constitutes liver cancer heterogeneity, play a vital role in cancer initiation, invasion, recurrence, metastasis, and resistance to chemo-radiotherapy. It is believed that therapies targeting LCSCs can improve the efficacy of conventional chemotherapy and radiotherapy by completely eliminating tumors while preventing recurrence. Therefore, during last decades, numerous surface markers for LCSCs have been identified and characterized in many subtypes of liver cancer, especially in hepatocellular carcinoma (HCC). These well-recognized surface markers significantly promote the therapeutic efficacy that identifies, targets and destroys LCSCs. Meanwhile, there have been intensive studies that aim to investigate the molecular mechanism of how stemness contributes to liver cancer relapse, recurrence and resistance. However, liver cancer stemness seems to be regulated by a hierarchical organization and crosstalk of a wide variety of signaling pathways. Using individual or few LCSC surface markers may not be able to completely reveal the intrinsic stemness hierarchy. From an integrated perspective, understanding of recent advances in LCSC surface markers remains important and urgent. In this review, we concentrate on demonstrating the indispensable roles of LCSC surface markers in identification and characterization of multiple cancer stages including initiation, invasion, metastasis, resistance and highlighting the cutting-edge therapeutic strategies against cancer stem cells in HCC.

Cancer stem cells in hepatocellular carcinoma — from origin to clinical implications

“…In fact, many of the liver CSC markers identified in HCC are oncofetal markers shared by hepatoblasts and hepatic progenitor cells. Our current knowledge of liver CSC cell surface markers including CD133, CD44, CD24, EpCAM, CD90, CD13, CD47, ICAM-1, LGR5 and calcium channel α2δ1; drug efflux markers including Side Population (SP), ABCB5 and aldehyde dehydrogenase (ALDH); as well as intracellular marker like keratin 19 (K19) have been comprehensively elsewhere 3,4 and summarized in Table 1.…”

Targeting the mechano-microenvironment and liver cancer stem cells: a promising therapeutic strategy for liver cancer

“…Nearly 20 molecular markers have been identified to isolate and characterize LCSCs 52 . Other studies have summarized LCSC surface markers in detail 13,[52][53][54][55] . Surface markers, such as CD13, CD44, EpCAM, CD90, CD24, CD34, CD47, ICAM1, EpCAM, LGR5, and OV6, are widely recognized as markers of LCSCs, because of their association with proliferative capacity, self-renewal capacity, drug resistance, and recurrence of liver cancer.…”

Complex Tumor Spheroid Formation and One-Step Cancer-Associated Fibroblasts Purification from Hepatocellular Carcinoma Tissue Promoted by Inorganic Surface Topography

“…As the spheroids were AFP-positive tumor cells, fresh CAF isolates from 3 HCC patients were analyzed by fluorescence-activated cell sorting (FACS) for contaminating non-CAF cells (Table 1). In the three CAF isolates from HCC derived from patient 1-3 cancer stem cells (CSC) positive for CD13 [48,49], CD44, CD90 [49], CD133 [50], OV6 [49], epithelial cells or CSCs positive for EpCAM [49], or general tumor cells positive AFP [51] were identified by immunofluorescence. This confirmed that the CAF isolates still contained different amounts of contaminating cells, especially varying concentrations of CSC.…”