Significance of CD90+ Cancer Stem Cells in Human Liver Cancer

Yang, Zhen; Ho, David W.; Ng, Michael; Lau, Chi Keung Marco; Yu, Wan; Ngai, Patricia; Chu, Patrick; Lam, Chi Tat; Poon, Ronnie T. P.; Fan, Sheung Tat

doi:10.1016/j.ccr.2008.01.013

Cited by 1,083 publications

(916 citation statements)

References 54 publications

(52 reference statements)

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“…This suggests that CD90 may not be the single marker representing the CSCs of all gastric cancers, owing to the heterogeneity of the gastric cancers, as well as antecede evidence from other studies (Bowles and Benjamin, 2001;Takaishi et al, 2008). A similar multimarker hypothesis has been suggested for CSCs in breast, liver and pancreatic cancers (Al-Hajj et al, 2003;Li et al, 2007;Yang et al, 2008). ERBB2 overexpression could also contribute to the difference in the tumorigenicity of the CD90 þ cells isolated from different primary tumor models.…”

Section: Discussionmentioning

confidence: 81%

“…Several studies have also identified Notch1 and ALDH1 as markers in both normal and malignant stem and progenitor cells (Dontu et al, 2004;Matsui et al, 2004;Ginestier et al, 2007). Yang et al (2008) first suggested CD90 to be a potential marker for liver CSCs. Interestingly, in addition to CD90 being highly enriched in cells cultured under sphere conditions, the percentage of CD90 þ cells in the population correlated closely with the tumorigenicity of the gastric primary tumor models.…”

Section: Discussionmentioning

confidence: 99%

“…Its expression has been found in bone marrowderived mesenchymal stem cells (Dennis et al, 2007), hepatic stem/progenitor cells (La´zaro et al, 2003;Dan et al, 2006;Herrera et al, 2006), hematopoietic stem cells and keratinocytic stem cells (Nakamura et al, 2006;Araki et al, 2007;Haack-Sorensen et al, 2007). It has also been identified in human liver CSCs, murine breast CSCs and primarily cultured CD133 þ glioblastoma CSCs (Liu et al, 2006;Cho et al, 2008;Yang et al, 2008). CD90 was found to be expressed in 95% of clinical gastric tumor samples by immunohistochemical staining (Oikonomou et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Trastuzumab (herceptin) targets gastric cancer stem cells characterized by CD90 phenotype

et al. 2011

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Identification and characterization of cancer stem cells (CSCs) in gastric cancer are difficult owing to the lack of specific markers and consensus methods. In this study, we show that cells with the CD90 surface marker in gastric tumors could be enriched under non-adherent, serumfree and sphere-forming conditions. These CD90 þ cells possess a higher ability to initiate tumor in vivo and could re-establish the cellular hierarchy of tumors from singlecell implantation, demonstrating their self-renewal properties. Interestingly, higher proportion of CD90 þ cells correlates with higher in vivo tumorigenicity of gastric primary tumor models. In addition, it was found that ERBB2 was overexpressed in about 25% of the gastric primary tumor models, which correlates with the higher level of CD90 expression in these tumors. Trastuzumab (humanized anti-ERBB2 antibody) treatment of hightumorigenic gastric primary tumor models could reduce the CD90 þ population in tumor mass and suppress tumor growth when combined with traditional chemotherapy. Moreover, tumorigenicity of tumor cells could also be suppressed when trastuzumab treatment starts at the same time as cell implantation. Therefore, we have identified a CSC population in gastric primary tumors characterized by their CD90 phenotype. The finding that trastuzumab targets the CSC population in gastric tumors suggests that ERBB2 signaling has a role in maintaining CSC populations, thus contributing to carcinogenesis and tumor invasion. In conclusion, the results from this study provide new insights into the gastric tumorigenic process and offer potential implications for the development of anticancer drugs as well as therapeutic treatment of gastric cancers.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Trastuzumab (herceptin) targets gastric cancer stem cells characterized by CD90 phenotype

et al. 2011

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“…Recent studies demonstrated that the CD90 marker was expressed on hepatic stem/ progenitor cells during liver development (33) and in a stem cell population from human adult liver (34,35). In cancer, Yang et al (36) found that CD90 expression correlated with the tumorigenic potential of hepatocellular carcinoma cell lines and suggested CD90 as a putative marker for liver CSCs. Furthermore, Liu et al (37) demonstrated that CD133 1 glioblastoma CSCs from primary cultures presented high levels of CD90 mRNA and were resistant to several chemotherapeutic agents.…”

Section: Discussionmentioning

confidence: 99%

Differential expression of CD90 and CD14 stem cell markers in malignant breast cancer cell lines

et al. 2012

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The recently emerged concept of cancer stem cell (CSC) has led to a new hypothesis on the basis for tumor progression. Basically, the CSC theory hypothesizes the presence of a hierarchically organized and relatively rare cell population, which is responsible for tumor initiation, self-renewal, and maintenance, in addition to accumulation of mutation and resistance to chemotherapy. CSCs have recently been described in breast cancer. Different genetic markers have been used to isolate breast CSCs, none of which have been correlated with the tumorigenicity or metastatic potential of the cells, limiting their precise characterization and clinical application in the development of therapeutic protocols. Here, we sought for subpopulations of CSCs by analyzing 10 judiciously chosen stem cell markers in a normal breast cell line (MCF10-A) and in four human breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-435, and Hs578-T) displaying different degrees of metastatic and invasiveness potential. We were able to identify two markers, which are differentially expressed in nontumorigenic versus tumor cells. The CD90 marker was highly expressed in the malignant cell lines. Interestingly, the CD14 molecule displayed higher expression levels in the nontumorigenic cell line. Therefore, we demonstrated that these two markers, which are more commonly used to isolate and characterize stem cells, are differentially expressed in breast tumor cells, when compared with nontumorigenic breast cells. ' 2012 International Society for Advancement of Cytometry Key terms CD90; Thy-1; breast cancer; cancer stem cell; CD14; breast cancer stem cell

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“…Mishra and colleagues [28] have suggested that HCC CSCs are descendents of normal parenchymal stem cells that have lost sensitivity to the inhibitory growth effects of TGFβ, while cell selection based on Thy-1 (CD90), a disputed marker of oval cells (see Table 2), in combination with CD44, has also produced cells with aggressive tumorigenic potential [160,161]. It remains to be seen how much overlap there is between these various markers, or whether there is a 'one-fits-all' marker for CSCs in HCC and indeed in other tumour types as well.…”

Section: Mr Alison Et Almentioning

confidence: 99%

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

Alison

Islam

Lim

2008

The Journal of Pathology

199

149

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The worldwide shortage of donor livers to transplant end stage liver disease patients has prompted the search for alternative cell therapies for intractable liver diseases, such as acute liver failure, cirrhosis and hepatocellular carcinoma (HCC). Under normal circumstances the liver undergoes a low rate of hepatocyte 'wear and tear' renewal, but can mount a brisk regenerative response to the acute loss of two-thirds or more of the parenchymal mass. A body of evidence favours placement of a stem cell niche in the periportal regions, although the identity of such stem cells in rodents and man is far from clear. In animal models of liver disease, adopting strategies to provide a selective advantage for transplanted hepatocytes has proved highly effective in repopulating recipient livers, but the poor success of today's hepatocyte transplants can be attributed to the lack of a clinically applicable procedure to force a similar repopulation of the human liver. The activation of bipotential hepatic progenitor cells (HPCs) is clearly vital for survival in many cases of acute liver failure, and the signals that promote such reactions are being elucidated. Bone marrow cells (BMCs) make, at best, a trivial contribution to hepatocyte replacement after damage, but other BMCs contribute to the hepatic collagen-producing cell population, resulting in fibrotic disease; paradoxically, BMC transplantation may help alleviate established fibrotic disease. HCC may have its origins in either hepatocytes or HPCs, and HCCs, like other solid tumours appear to be sustained by a minority population of cancer stem cells.

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Significance of CD90+ Cancer Stem Cells in Human Liver Cancer

Cited by 1,083 publications

References 54 publications

Trastuzumab (herceptin) targets gastric cancer stem cells characterized by CD90 phenotype

Trastuzumab (herceptin) targets gastric cancer stem cells characterized by CD90 phenotype

Differential expression of CD90 and CD14 stem cell markers in malignant breast cancer cell lines

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

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