Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97

Li, Y; Tang, Zhao–You; Ye, S L; Liu, Y K; Chen, J; Qin, Xue; Gao, Dongmei; Bao, Wei-Hua

doi:10.3748/wjg.v7.i5.630

Cited by 314 publications

(120 citation statements)

References 51 publications

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“…In our study, we also found that all cases with lymph node metastasis occurred in patients with positive HIWI expression, although sample size bias could not be completely excluded. Moreover, we found that both mRNA and protein levels of HIWI expression were up‐regulated in 3 high metastatic potential HCC cell lines that were isolated from the same parent cell MHCC97 28. Interestingly, HIWI expression was not different among these HCC cell lines with different metastatic potential.…”

Section: Discussionmentioning

confidence: 83%

HIWI is associated with prognosis in patients with hepatocellular carcinoma after curative resection

Zhao

Zhou

Wang

et al. 2011

Cancer

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BACKGROUND: PIWI protein family was found to play an important role in stem cell self-renewal. Overexpression of HIWI, the human homolog of PIWI family proteins, was found in several solid tumors, although the role of HIWI in hepatocellular carcinoma (HCC) and its prognostic value remain unclear. METHODS: HIWI expression was measured in stepwise metastatic HCC cell lines (HCCLM3, MHCC97H, MHCC97L, SMMC7721, and HepG2), the normal liver cell line (L02), and HCC tissue samples (n ¼ 20). Proliferation and invasion were investigated in HCC cell lines undergoing HIWI target small interfering RNA transfection. Also explored was HIWI expression in HCC tissue microarrays (n ¼ 168) for survival analysis. RESULTS: Levels of HIWI protein and mRNA were up-regulated in highly metastatic HCC cell lines (HCCLM3, MHCC97H, and MHCC97L), whereas their proliferation and invasion significantly decreased after depletion of HIWI. Intratumoral HIWI expression was higher than that of peritumoral tissue (P < .001) and positively associated with proliferating cell nuclear antigen expression (P < .001). Positive expression of intratumoral HIWI was associated with larger tumor size (P ¼ .047) and intrahepatic metastasis (P ¼ .027) and was an independent risk factor for overall survival (P ¼ .007) and recurrence-free survival (P ¼ .036), particularly in patients with low serum afetoprotein and low Edmondson-Steiner grade. CONCLUSIONS: HIWI may play a key role in HCC proliferation and metastasis and can be a potential prognostic factor for HCC after curative resection, particularly with well-differentiated HCC.

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Section: Discussionmentioning

confidence: 83%

HIWI is associated with prognosis in patients with hepatocellular carcinoma after curative resection

Zhao

Zhou

Wang

et al. 2011

Cancer

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“…C, P > .05). Furthermore, we examined the SIN1 expression in 6 liver cell lines, including a normal liver cell line (L02 cells), and 5 HCC cell lines with different metastatic potential (HepG2, MHCC97‐L, MHCC97‐H, SMMC‐7721, and HCCLM3) . Either real‐time qRT‐PCR or western blot showed that the SIN1 expression levels were significantly higher in HCC cell lines than those in normal liver cells (LO2) (Fig.…”

Section: Resultsmentioning

confidence: 99%

SIN1 promotes invasion and metastasis of hepatocellular carcinoma by facilitating epithelial‐mesenchymal transition

Yang

et al. 2013

Cancer

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BACKGROUND: Stress-activated protein kinase (SAPK) interacting protein 1 (SIN1) is essential for early embryonic development and is the key regulator of Akt, which plays an important role in various pathological conditions such as cancer. However, the biological function and clinical significance of SIN1 in hepatocellular carcinoma (HCC) remains unknown. METHODS: Real-time quantitative reverse-transcriptase polymerase chain reaction analysis, western blot analysis, and immunohistochemical staining were used to test the expression level of SIN1, and its correlation with clinicopathologic parameters as well as the prognosis for patients with HCC were analyzed. In addition, the biological function and molecular mechanisms of SIN1 in HCC were investigated. RESULTS: SIN1 levels were elevated predominantly in HCC tissues, and its level in solitary large HCC was significantly lower than those in nodular HCC (P 5.016), but showed no significant differences between solitary large HCC and small HCC (P >.05). Levels of SIN1 were up-regulated in highly metastatic HCC cell lines (HCCLM3 and MHCC97-H), whereas their invasion and migration significantly decreased after depletion of SIN1. High expression of SIN1 was associated with tumor number (P 5.012), capsular formation (P 5.037), and venous invasion (P 5.023) and was an independent risk factor for overall survival (P 5.046). Finally, SIN1 was capable of promoting invasion and metastasis of HCC by facilitating epithelial-mesenchymal transition. CONCLUSIONS: The current findings suggest that SIN1 plays an important role in HCC invasion and metastasis by facilitating epithelial-mesenchymal transition. Cancer 2013;119:2247-57. V C 2013 American Cancer Society.KEYWORDS: SAPK interacting protein 1; hepatocellular carcinoma; invasion; metastasis; epithelial-mesenchymal transition. INTRODUCTIONHepatocellular carcinoma (HCC) is one of the most common cancers and ranks as the second leading cause of cancerrelated death in men worldwide. 1,2 The overall survival of patients with HCC remains unsatisfactory because of a high incidence of recurrence and metastasis. 3,4 In recent decades, various molecules have been reported to play a role in invasion and migration of HCC, such as RhoC, Egfl7, FBI-1, and HSF1. 5-8 Although these findings represent significant progress in the field, the mechanisms underlying HCC metastasis are still largely unknown. Therefore, it is very important to identify the effective biomarkers to predict outcome and prevent postoperative recurrence and metastasis of HCC.Previous studies showed that SAPK interacting protein 1 (SIN1) is essential for early embryonic development and is the key regulator of Akt which play an important role in various pathological conditions such as cancer. 9-11 SIN1 was identified as a key TORC2 component and regulator of the Akt pathway that positively controls Akt-Ser473 phosphorylation and activation. However, the biological function and clinical significance of SIN1 in HCC remains unknown.Therefore, we carried out the current study...

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“…Recently, a metastatic human HCC tumor model (LCI-D20) has been developed in our institute based on the formation of tumors in nude mice using a battery of HCC cell lines with median (MHCC97), low (MHCC97-L) or high (MHCC97-H) metastatic potential [1, 2, 3]. MHCC97 tumors showed responses to IFN-α treatment including inhibition of tumor growth, recurrence and metastasis.…”

Section: Introductionmentioning

confidence: 99%

Reduction in p48-ISGFγ Levels Confers Resistance to Interferon-α<sub>2a</sub> in MHCC97 Cells

Sun

Gao

et al. 2004

Oncology

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Objectives: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies in China and, due to the limited efficacy of currently available therapies, is responsible for a large number of deaths. IFN-α therapy has shown promise in the treatment of various forms of human cancer and is considered in the treatment of HCC. Previous results from our group showed that high doses of IFN-α exert a significant antiproliferative effect on MHCC97 human xenografts in nude mice, but not on MHCC97 cells when tested in vitro. Here we present experiments designed to characterize the molecular mechanism underlying the defective response of MHCC97 cells to IFN-α. Elucidation of the mechanism underlying the defective response of MHCC97 to IFN-α may help to explain and possibly to overcome clinical failures of this form of tumor therapy. Methods: IFN-α_2a was administered between 3,000 and 10,000 IU/ml, a range strongly inhibiting proliferation in other cell lines. Gene expression profiles of MHCC97 cells were obtained before and after treatment with IFN-α_2a using cDNA microarray analysis. The transcriptional activity of relevant genes responding to IFN-α_2a in the cDNA microarray experiments was confirmed by RT-PCR and Northern blot analysis. Transient transfection with an expression vector was used to restore p48-ISGFγ (IRF9) protein levels. Cell proliferation was evaluated using the MTT assay. Results: Although IFN-α treatment caused the activation of several signal transduction pathways in MHCC97 cells, the lack of an antiproliferative effect was found to mainly derive from a defect in the activation of the transcription factor ISGF3 required for Jak/STATS signaling. We show that the defect in ISGF3 activation is mainly caused by the absence of one of its essential components, the protein p48-ISGFγ from MHCC97 cells. Indeed, transient expression of p48-ISGFγ restores sensitivity to IFN-α_2a. Although the mRNA levels of p48-ISGFγ were normal in MHCC97 cells, mutations could be detected in the gene coding for the protein. We hypothesize, therefore, that these mutations alter the message or protein stability, leading to the reduced protein levels observed. Conclusion: Our results confirm the important role of Jak/STATS signaling in the antiproliferative effects of IFN-α in tumor cells and indicate that defects in ISGF3 can cause resistance to IFN-α_2a treatment.

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Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97

Cited by 314 publications

References 51 publications

HIWI is associated with prognosis in patients with hepatocellular carcinoma after curative resection

HIWI is associated with prognosis in patients with hepatocellular carcinoma after curative resection

SIN1 promotes invasion and metastasis of hepatocellular carcinoma by facilitating epithelial‐mesenchymal transition

Reduction in p48-ISGFγ Levels Confers Resistance to Interferon-α<sub>2a</sub> in MHCC97 Cells

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