Disseminated tumor cells homing into rats’ liver: A new possible mechanism of HCC recurrence

Li, Qigen; Yang, Guanhu; Yang, Qing; Wei, Lixin; Yang, Ning; Zhou, Xiaozhu; Jia, Feng-Qi

doi:10.3748/wjg.v10.i6.903

Cited by 7 publications

(8 citation statements)

References 22 publications

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“…As is well known, the recipient's circulating tumor cells deposit in the donor liver and interact with the microenvironment, which subsequently results in the intrahepatic recurrence of HCC . The interaction between tumor cells and stromal cells plays a key role in all aspects of cancer biology including transformation, proliferation and invasion .…”

Section: Discussionmentioning

confidence: 99%

“…Second, de novo carcinogenesis may occur in the donor liver, but this is much less likely. In either case, the hepatic microenvironment (soil) plays an important role in the behavior of cancer cells (seeds) and in tumor recurrence . As the donor liver could bring disease‐susceptibility genes and increase the risk of new‐onset diabetes mellitus after LT, we hypothesize that the donor liver may provide a HCC‐susceptible environment, which contributes to HCC recurrence after transplantation.…”

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confidence: 99%

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Donor miR‐196a‐2 polymorphism is associated with hepatocellular carcinoma recurrence after liver transplantation in a Han Chinese population

Ling

Wang

et al. 2015

Intl Journal of Cancer

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Recurrence of hepatocellular carcinoma (HCC) is one of the leading causes of death after liver transplantation (LT). We aim to evaluate the association of donor and recipient single nucleotide polymorphisms (SNPs) with the risk of HCC recurrence after LT. A total of 155 adult patients who underwent primary LT for HCC were enrolled. Ten SNPs associated with HCC susceptibility were genotyped. Patients who received donor livers with the rs11614913 homozygous CC variant presented significantly higher recurrence rates of HCC (41.7 vs. 15.3%, p 5 0.009) and lower cumulative tumor-free survival (p 5 0.005) than those who received TT wild-type donor livers. The donor rs11614913 genetic variant was an independent risk factor for HCC recurrence (odds ratio 5 2 per each C allele, p < 0.05) and could significantly improve the predictive abilities of clinical models (Milan, UCSF and Hangzhou criteria). Donor livers homozygous for rs11614913 CC were associated with a higher miR-196a expression than TT (p 5 0.002). In a lentiviral infection of mouse liver and orthotopic mouse model of HCC, the liver miR-196a overexpression group showed a significantly larger tumor size than the control group (p 5 0.001). There is a close association between the tumor size and expression of miR-196a in the liver (r 5 0.693, p 5 0.001). In conclusion, the donor miR-196a-2 rs11614913 polymorphism is associated with HCC recurrence after LT and improves the predictive value of clinical models. The overexpression of miR-196a in the liver might provide a tumor-favorable environment for the development of HCC.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Donor miR‐196a‐2 polymorphism is associated with hepatocellular carcinoma recurrence after liver transplantation in a Han Chinese population

Ling

Wang

et al. 2015

Intl Journal of Cancer

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“…The postoperative recurrence rate is 65% with radical resection and 58% with liver transplantation. 10 Furthermore, the resistance of some HCC patients to conventional chemotherapy contributes to the poor prognosis and high mortality associated with this disease. 11 The new concept of cancer stem cells (CSCs) was recently put forward in an attempt to elucidate the mechanism of HCC chemoresistance, metastasis and recurrence.…”

Section: Introductionmentioning

confidence: 99%

Attenuated Listeria monocytogenes as a cancer vaccine vector for the delivery of CD24, a biomarker for hepatic cancer stem cells

Hou

Zhe

et al. 2014

Cell Mol Immunol

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Attenuated Listeria monocytogenes (LM) is a promising candidate vector for the delivery of cancer vaccines. After phagocytosis by antigen-presenting cells, this bacterium stimulates the major histocompatibility complex (MHC)-I and MHC-II pathways and induces the proliferation of antigen-specific T lymphocytes. A new strategy involving genetic modification of the replication-deficient LM strain DdalDdat (Lmdd) to express and secrete human CD24 protein has been developed. CD24 is a hepatic cancer stem cell biomarker that is closely associated with apoptosis, metastasis and recurrence of hepatocellular carcinoma (HCC). After intravenous administration in mice, Lmdd-CD24 was distributed primarily in the spleen and liver and did not cause severe organ injury. Lmdd-CD24 effectively increased the number of interferon (IFN)-c-producing CD8 1 T cells and IFN-c secretion. Lmdd-CD24 also enhanced the number of IL-4-and IL-10-producing T helper 2 cells. The efficacy of the Lmdd-CD24 vaccine was further investigated against Hepa1-6-CD24 tumors, which were inguinally inoculated into mice. Lmdd-CD24 significantly reduced the tumor size in mice and increased their survival. Notably, a reduction of T regulatory cell (Treg) numbers and an enhancement of specific CD8 1 T-cell activity were observed in the tumor-infiltrating lymphocytes (TILs). These results suggest a potential application of the Lmdd-CD24 vaccine against HCC.

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“…The way in which primary liver tumors metastasize and relapse is still debated (Fukutomi et al, 2001;Li et al, 2004). Liver cancers can be treated by orthotopic liver transplantation.…”

Section: Introductionmentioning

confidence: 99%

Fate and characterization of circulating tumor cells in a NOD/SCID mouse model of human hepatocellular carcinoma

et al. 2006

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There is much debate about the way in which epithelial tumors metastasize. It has been proposed that the bone marrow (BM) acts as a tumor cell reservoir. We injected human hepatocellular carcinoma (HCC) cells (Mahlavu cell line) into the livers, circulation or BM of NOD/SCID mice and circulating tumor cells were quantified. When injected under the Glisson capsule, a primary tumor developed and continuously yielded circulating tumor cells. Liver tumor removal led to a very low level of Mahlavu cells both in blood and BM 30 days later. When Mahlavu cells (cultured or from BM of primary mice femurs) were intravenously injected into mice, the number of cells in the bloodstream (BS) steadily decreased, whereas the BM was not significantly colonized. When Mahlavu cells were directly injected into one femur, the controlateral femur was not colonized. Microscopic analysis and a sensitive PCR assay (o1 Mahlavu cell/ nuclear cells) both failed to detect human tumor cells in other organs regardless of injection route. In conclusion, our model strongly supports the hypothesis that HCCs continuously release cells into the BS. However, in sharp contrast with the current hypothesis, the BM is not specifically colonized by tumor cells but could store them at a very low level.

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Disseminated tumor cells homing into rats’ liver: A new possible mechanism of HCC recurrence

Abstract: AIM:To detect the origin of hepatocellular carcinoma (HCC) recurring and attempt to propose a new recurrent mechanism.

Cited by 7 publications

References 22 publications

Donor miR‐196a‐2 polymorphism is associated with hepatocellular carcinoma recurrence after liver transplantation in a Han Chinese population

Donor miR‐196a‐2 polymorphism is associated with hepatocellular carcinoma recurrence after liver transplantation in a Han Chinese population

Attenuated Listeria monocytogenes as a cancer vaccine vector for the delivery of CD24, a biomarker for hepatic cancer stem cells

Fate and characterization of circulating tumor cells in a NOD/SCID mouse model of human hepatocellular carcinoma

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