Side population in hepatocellular carcinoma HCCLM3 cells is enriched with stem-like cancer cells

Abstract

Abstract. Substantial evidence implicates that low-abundance cancer stem cells (CSCs) are responsible for tumor metastasis and recurrence in hepatocellular carcinoma (HCC). Side population (SP) cells possess typical CSCs-like features, and are frequently considered as a special subpopulation in which CSCs are enriched and in studies may be considered as a substitute for CSCs. The aim of the present study was to examine the abundance of SP cells in human HCC cell lines with different metastatic potentials and compare their CSC-like, tumorigenic and invasive properties with those of the main population (MP) cells. An experimental system is described for identifying SP cells and analyzing their CSC-like properties. The relative abundance of SP cells correlated directly with the metastatic potential of the HCC cell line: HCCLM3, 16.3±2.2%; MHCC97-H, 8.4±0.7%; MHCC97-L, 4.7±0.5%; and Huh7, 1.0±0.3% (P<0.05). SP cells isolated from HCCLM3 cultures showed significantly higher proliferation rates and clonogenicity than the corresponding MP cells, in addition to higher migration and invasive abilities in vitro and greater tumorigenicity in mice. Expression levels of all CSC-associated genes tested, except EpCAM and Oct4, were significantly higher in SP cells. The findings revealed that the proportion of SP cells correlates with metastatic potential, and SP cells demonstrated the characteristics expected of CSCs, implicating them in HCC metastasis. Further studies on the identification and characterization of SP cells using clinical HCC specimens will contribute to the understanding of how SP cells are involved in these disease processes.

CPEB1 mediates hepatocellular carcinoma cancer stemness and chemoresistance

“…Increasing evidence suggests that a subpopulation of cells that exhibit stem cell properties may give rise to HCC and lead to an increase in proliferation, metastasis and chemoresistance 27 – 29 . Furthermore, a subpopulation of cells in the human HCC cell lines MHCC97-H, MHCC97-L, Huh7 and HCCLM3 were found to initiate tumorigenesis when grafted into mice 9 . Therefore, finding a way to regulate subpopulations of CSCs in HCC could lead to an improved response to therapy.…”

“…The heterogeneity of HCC has previously been attributed to hepatocytes because the liver is thought to lack a defined stem cell population for organ maintenance 8 . However, growing evidence indicates that a distinct subpopulation of cells in liver tumors exhibit properties that are consistent with stemness 9 , 10 . Furthermore, high expression levels of CSC markers, such as OCT4, NANOG, SOX2 and LIN28, have been found in subpopulations of some HCC cell lines 11 , 12 .…”

Signaling pathway of globo-series glycosphingolipids and β1,3-galactosyltransferase V (β3GalT5) in breast cancer

“…SSEA3 has a higher percentage of expression (77.5%) than Globo-H (61%) in clinical breast cancer specimens (2) and in nonsmall cell lung cancer cells with multiple drug resistance (9), and the potential of tumorigenesis and sphere formation of colorectal cancer cells is enhanced with increasing SSEA3 expression (10). In addition, the enzymatic activity of β3GalT5 in the sera from clinical ovarian cancer and uterine cervical cancer patients is associated with cancer progression (11), and the expression of β3GalT5 is up-regulated in metastatic hepatocellular carcinoma HCCLM3 cells (12) and liver cancer-initiating cells (13). We also find that knockdown of β3GalT5 inhibited cell proliferation and induced caspase-3-mediated apoptosis in breast cancer cells (4), suggesting that the tumorigenicity and multidrug resistance of cancer cells may correlate with the expression of SSEA3.…”

Kaempferol and docetaxel diminish side population and down-regulate some cancer stem cell markers in breast cancer cell line MCF-7

“…High expression and activity of membrane transporters belonging to ABC transporter family are common features of CSCs that makes them multidrug-resistant. SP cells, which are a population with overexpression of ABC transports have many characteristics of CSCs (Guo et al, 2016;Litman et al, 2000). Hence, SP analysis has also been used here to study the effect of docetaxel and kaempferol on breast CSCs.…”