Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties

ABC transporters, neural stem cells and neurogenesis – a different perspective

“…Moreover, different research teams have demonstrated that ABCA3 and ABCG2 were expressed at higher levels in SP cells than in non-SP cells in human, rhesus monkey and mouse hematopoietic tissues; and microarray analysis indicated that several genes related to stem cells were substantially upregulated in the SP cells in comparison to non-SP cells [130,151,152]. This SP phenotype is present in several kinds of stem cells from different tissues, including the hematopoietic, meschenchymal, heart, liver, and pancreatic stem cells; it disappears with verapamil treatment thus indicating that the SP phenotype might result from the expression of ABC transporters in a primitive subset of stem cells in mammals [140,142,131,145,146,148,153,154]. Since SP stem cells show high repopulating activity and ABCA3, ABCB1 and ABCG2 expression, it has been hypothesized that the special phenotype of SP cells might be controlled or regulated by the expression of ABC transporters [142,144,145,149,155,156].…”

“…Later Goodell et al [9] demonstrated that a highly enriched stem cell fraction termed SP could be isolated following Hoechst-33342 staining. Recently, ABCA3, ABCB1 and ABCG2 were found in the primitive stem cells of different tissues [129][130][131][132][133][134][135][136]. In particular, ABCB1 is expressed in human CD34+ stem cells, which can be identified by their ability to transport fluorescent dyes like Rh123 and Hoechst-33342 [128,129,[137][138][139][140][141][142][143].…”

“…In particular, ABCB1 is expressed in human CD34+ stem cells, which can be identified by their ability to transport fluorescent dyes like Rh123 and Hoechst-33342 [128,129,[137][138][139][140][141][142][143]. Interestingly, the SP phenotype in rodent and human tissues often appears to be specifically determined by the expression of an ABC transporter: for example, both ABCB1 and ABCG2 transporters are highly expressed in the SP of stem cells from different tissues such as brain, bone marrow, pancreas, liver and others, all of which can be isolated based on the cells' ability to promote the efflux of the Hoechst-33342 fluorescent dye [9,[129][130][131][132][133][134][135][136][142][143][144][145][146][147][148][149][150]. Moreover, different research teams have demonstrated that ABCA3 and ABCG2 were expressed at higher levels in SP cells than in non-SP cells in human, rhesus monkey and mouse hematopoietic tissues; and microarray analysis indicated that several genes related to stem cells were substantially upregulated in the SP cells in comparison to non-SP cells [130,151,152].…”

“…In vivo propagation of leukemias, such as AML-SP1, is a model system of maintaining the population heterogeneity of the AML disease, especially the unique characteristics of leukemic SP cells [142]. In another study, Chiba et al [131] reported that the SP phenotype of stem-like cells isolated from hepatocellular carcinoma seemed not to be related to ABCG2 (Bcrp1), but rather to several other ABC transporters, notably ABCB1 (MDR1), ABCB2, ABCC7 and ABCA5, as they found a several fold upregulation of expression of these genes in "PLC/PRF/5"-SP cells as compared to non-SP cells.…”

Stem cells in liver regeneration, fibrosis and cancer: the good, the bad and the ugly

“…Chiba and colleagues [154] have reported that two of the four HCC cell lines that they studied had SP cells comprising 0.25% and 0.8% of the cell population. These cells were highly proliferative and relatively resistant to apoptosis in vitro.…”