Liver cancer stem cells are selectively enriched by low-dose cisplatin

Zhang, H.; Chang, Wen-Yi; Li, X.Y.; Zhang, N.; Kong, Jianyi; Wang, Y.F.

doi:10.1590/1414-431x20143415

Cited by 11 publications

(7 citation statements)

References 20 publications

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“…Those findings may be explained by our results described here regarding the preferential targeting of SCLCCs by PIM inhibition. Cisplatin enriches the frequency of cancer stem cells in hepatocellular carcinoma [49] . By giving cisplatin to target the non-SCLCCs and increase the frequency of SCLCCs alongside AZD1208 to target the SCLCCs, we may be able to more effectively treat hepatoblastoma and eradicate SCLCCs.…”

Section: Discussionmentioning

confidence: 99%

Targeting PIM Kinases Affects Maintenance of CD133 Tumor Cell Population in Hepatoblastoma

Stafman

Williams

Garner

et al. 2019

Translational Oncology

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Hepatoblastoma is the most common primary liver tumor in children, but treatment has not changed significantly in the past 20 years. We have previously demonstrated that Proviral Integration site for Moloney murine leukemia (PIM) kinases promote tumorigenesis in hepatoblastoma. Stem cell-like cancer cells (SCLCCs) are a subset of cells thought to be responsible for chemoresistance, metastasis, relapse, and recurrence. The aim of this study was to identify SCLCCs in hepatoblastoma and determine the role of PIM kinases in SCLCCs. Hepatoblastoma cells were separated into CD133-enriched and CD133-depleted populations and the frequency of SCLCCs was assessed. CD133 expression was determined in the presence or absence of the PIM inhibitor, AZD1208. The effects of AZD1208 on proliferation, apoptosis, and motility were assessed in vitro and the effect of AZD1208 on tumor growth was examined in vivo. We identified CD133 as a marker for SCLCCs in hepatoblastoma and showed that PIM kinases promote a SCLCC phenotype. PIM kinase inhibition with AZD1208 decreased proliferation, migration, and invasion and increased apoptosis in both SCLCCs and non-SCLCCs in a long-term passaged hepatoblastoma cell line and patient-derived xenograft. Additionally, tumor growth in mice implanted with hepatoblastoma SCLCCs was decreased with PIM inhibition such that 57% of the tumors regressed. These findings identify CD133 as a marker for SCLCCs in hepatoblastoma and provide evidence that inhibition of PIM kinases decreases stemness and tumorigenicity of SCLCCs in hepatoblastoma, making them potential therapeutic targets for the treatment of hepatoblastoma.

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Section: Discussionmentioning

confidence: 99%

Targeting PIM Kinases Affects Maintenance of CD133 Tumor Cell Population in Hepatoblastoma

Stafman

Williams

Garner

et al. 2019

Translational Oncology

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“…It is believed that HCC is sustained by liver cancer stem cells (LCSCs), which constitute a relatively small frequency of cells, and they do so through their ability to propagate highly heterogeneous progeny, multi-drug resistance to chemotherapeutic agents and a high capacity for cellular proliferation (3). A number of studies have suggested that LCSCs can be identified by several cell surface antigens including CD133, CD44, and ALDH1 (4)(5)(6). Furthermore, CD133 + , CD44 + and ALDH1 + cells that are isolated from HCC cells display an enhanced capacity for malignant transformation in vivo.…”

Section: Introductionmentioning

confidence: 99%

Reversal of liver cancer-associated stellate cell-induced stem-like characteristics in SMMC-7721 cells by 8-bromo-7-methoxychrysin via inhibiting STAT3 activation

et al. 2016

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Hepatic stellate cells (HSCs) that are activated by human hepatocellular carcinoma (HCC) cells secrete a variety of cytokines, which are the main component of the HCC microenvironment. We aimed to determine whether 8-bromo-7-methoxychrysin (BrMC) could interfere in cross-talk of the human hepatic stellate cell line LX-2 and liver cancer stem-like cells (LCSLCs) to inhibit the characteristics of LCSLCs endowed with the capacity of sustaining human hepatocellular carcinoma (HCC) self-renewal and progression, and to identify its potential mechanism of action. We found that the levels of fibroblast activation protein (FAP) were augmented in LX-2 cells treated with the conditioned medium of LCSLCs (LCSLC-CM) compared to those cultured with routine medium, indicating that the LCSLC-CM can activate LX-2 cells to become liver cancer-associated stellate cells (LCAHSCs). Furthermore, sphere forming capability of SMMC-7721 cells was enhanced and stem cell-related protein expression was significantly increased following treatment with the conditioned medium of LCAHSCs (LCAHSC-CM). Moreover, the level of p-STAT3 was increased in LX-2 cells treated with LCSLC-CM and BrMC reduced expression of p-STAT3. Combination of BrMC and the selective inhibitor of STAT3 cucurbitacin I (JSI-124) synergistically suppressed the LCSLC characteristics in SMMC-7721 cells. Collectively, our data showed that BrMC inhibited the interaction between LX-2 cells and HCC-derived CSCs, and did so potentially through modulation of the STAT3 pathway. Future therapeutic strategies employing anti-CSC therapy should confirm the potential of cucurbitacin I (JSI-124) and BrMC as potent therapeutic agents.

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“…[29,30] Similarly to some other studies, our results showed that cisplatin and 5 FU significantly decreased tumor cell survival rate after 24 hours. [31] Although the majority of cancer cells died following 24-hour cisplatin therapy, a small population of cells survived suggesting resistance.…”

Section: Discussionmentioning

confidence: 99%

Characterization of stem‐like cancer cells in basal cell carcinoma and its surgical margins

Milošević

Lazarević

Toljic

et al. 2018

Experimental Dermatology

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Liver cancer stem cells are selectively enriched by low-dose cisplatin

Cited by 11 publications

References 20 publications

Targeting PIM Kinases Affects Maintenance of CD133 Tumor Cell Population in Hepatoblastoma

Targeting PIM Kinases Affects Maintenance of CD133 Tumor Cell Population in Hepatoblastoma

Reversal of liver cancer-associated stellate cell-induced stem-like characteristics in SMMC-7721 cells by 8-bromo-7-methoxychrysin via inhibiting STAT3 activation

Characterization of stem‐like cancer cells in basal cell carcinoma and its surgical margins

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