Sinusoidal endothelial cell progenitor cells promote tumor progression in the patients with hepatocellular carcinoma.

Abstract Objective: Since sinusoidal endothelial cell progenitor cells (SEPCs) play great roles in liver regeneration, it is necessary to elucidate that whether these SEPCs participate in tumor progression of hepatocellular carcinoma (HCC).Methods: A total of 45 patients with primary HCC, who received liver resection, were included in this study. The liver tumors were removed from patients and partial tissues were prepared to identify SEPCs by double staining of CD133/CD45 and CD133/CD31 at the same location. Blood samples were correspondingly collected to examine liver function parameters and tumor markers. The demographics and clinic-pathological characteristics of the patients were all collected for correlation analysis with SEPCs.Results: SEPCs were observed within abundant of blood vessels in HCC nodules of all the 45 patients, but no SEPCs were detected in the tumor-adjacent tissues. The number of SEPCs was correlated with the expression levels of HCC tumor markers α-fetoprotein (AFP) and CA199. There was a positive correlation between the expressions of SEPCs markers and the diameters of HCC tumors in differently differentiated specimens (P<0.01). The expressions levels of SEPCs markers in poorly differentiated HCC patients were significantly higher than those in the moderately and highly differentiated HCC patients (P<0.05).Conclusions: SEPCs are in close connection with HCC progression, and they may potentially act as prognosis and metastasis predicting index and even therapeutic candidates of HCC.

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Sinusoidal Endothelial Cell Progenitor Cells Promote Tumour Progression in Patients with Hepatocellular Carcinoma

Stem Cells International ◽

10.1155/2020/8819523 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Ya-xing Feng ◽

Wei Li ◽

Xu-dong Wen ◽

Ning Zhang ◽

Wei-hui Liu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Endothelial Cell ◽

Progenitor Cells ◽

Tumour Progression ◽

Clinicopathological Characteristics ◽

Tumour Markers ◽

Sinusoidal Endothelial Cell ◽

Liver Tumours ◽

Expression Levels ◽

Poorly Differentiated

Objective. As sinusoidal endothelial cell progenitor cells (SEPCs) play a significant role in liver regeneration, it is necessary to elucidate whether SEPCs participate in tumour progression of hepatocellular carcinoma (HCC). Methods. A total of 45 patients with primary HCC who underwent liver resection were included in this study. The liver tumours were removed from the patients, and partial tissues were prepared to identify SEPCs through double staining of CD133/CD45 and CD133/CD31 at the same location. Blood samples were collected to examine liver function parameters and tumour markers. The demographics and clinicopathological characteristics of the patients were collected for correlation analysis with SEPCs. Results. SEPCs were observed in several blood vessels within the HCC nodules of all 45 patients, but no SEPCs were detected in the tumour-adjacent tissues. The number of SEPCs was correlated with the expression levels of HCC tumour markers α-fetoprotein (AFP) and CA199. There was a positive correlation between the expression of SEPC markers and diameter of HCC tumours in differently differentiated specimens ( P < 0.01 ). The expression levels of SEPC markers were significantly higher in patients with poorly differentiated HCC than in patients with moderately and highly differentiated HCC ( P < 0.05 ). Conclusions. SEPCs are closely associated with HCC progression; therefore, SEPCs may be considered potential prognostic and metastatic biomarkers and therapeutic candidates for HCC.

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Role of tumor markers in assessment of tumor progression and prediction of outcomes in patients with hepatocellular carcinoma

Hepatology Research ◽

10.1111/j.1872-034x.2007.00181.x ◽

2007 ◽

Vol 37 (s2 Fourth JSH S) ◽

pp. S166-S171 ◽

Cited By ~ 22

Author(s):

Hidenori Toyoda ◽

Takashi Kumada ◽

Yukio Osaki ◽

Hiroko Oka ◽

Masatoshi Kudo

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Progression ◽

Tumor Markers

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Notch signaling inhibits hepatocellular carcinoma following inactivation of the RB pathway

Journal of Experimental Medicine ◽

10.1084/jem.20110198 ◽

2011 ◽

Vol 208 (10) ◽

pp. 1963-1976 ◽

Cited By ~ 125

Author(s):

Patrick Viatour ◽

Ursula Ehmer ◽

Louis A. Saddic ◽

Craig Dorrell ◽

Jesper B. Andersen ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Progenitor Cells ◽

Molecular Mechanisms ◽

Liver Tumors ◽

Expression Profiles ◽

Notch Pathway ◽

Gene Expression Profiles ◽

Feedback Mechanism ◽

Negative Feedback Mechanism ◽

Rb Pathway

Hepatocellular carcinoma (HCC) is the third cancer killer worldwide with >600,000 deaths every year. Although the major risk factors are known, therapeutic options in patients remain limited in part because of our incomplete understanding of the cellular and molecular mechanisms influencing HCC development. Evidence indicates that the retinoblastoma (RB) pathway is functionally inactivated in most cases of HCC by genetic, epigenetic, and/or viral mechanisms. To investigate the functional relevance of this observation, we inactivated the RB pathway in the liver of adult mice by deleting the three members of the Rb (Rb1) gene family: Rb, p107, and p130. Rb family triple knockout mice develop liver tumors with histopathological features and gene expression profiles similar to human HCC. In this mouse model, cancer initiation is associated with the specific expansion of populations of liver stem/progenitor cells, indicating that the RB pathway may prevent HCC development by maintaining the quiescence of adult liver progenitor cells. In addition, we show that during tumor progression, activation of the Notch pathway via E2F transcription factors serves as a negative feedback mechanism to slow HCC growth. The level of Notch activity is also able to predict survival of HCC patients, suggesting novel means to diagnose and treat HCC.

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Rare Gingival Metastasis by Hepatocellular Carcinoma

Case Reports in Medicine ◽

10.1155/2017/3192649 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Li-Jun Xue ◽

Xiao-Bei Mao ◽

Jian Geng ◽

Ya-Nan Chen ◽

Qian Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Histopathological Examination ◽

Cerebral Metastases ◽

Performance Score ◽

Intravenous Chemotherapy ◽

Pathological Characteristics ◽

Gingival Metastasis ◽

Sorafenib Therapy ◽

Multiple Metastases ◽

Poorly Differentiated

Hepatocellular carcinoma (HCC) uncommonly metastasizes to the gingiva, which always means a poor outcome. We reported a rare HCC case with multiple metastases to gingiva, lungs, and brain. A 60-year-old man was initially diagnosed as HCC with metastases to double lungs. He was subjected to a transarterial chemoembolization (TACE) (5-fluorouracil, 750 mg) and two cycles of intravenous chemotherapy (gemcitabine 1.8 g at days 1 and 8, oxaliplatin 200 mg at day 2, every 4 weeks). However, the volume of liver tumor still increased. A bean-size gingival nodule growing with occasional bleeding was also found. TACE (5-fluorouracil 750 mg, perarubicin 40 mg, cisplatin 20 mg) was performed again and an oral sorafenib therapy (400 mg, twice per day) was adopted. The disease maintained relatively stable for about 6 months until a second obvious progress. The gingival nodule was then palliatively excised and identified as a poorly differentiated metastatic HCC by histopathological examination. Best supportive treatments were made since the performance score was too bad. Finally, cerebral metastases occurred and the patient died of systemic failure. Upon review of previous reports, we discussed risk factors, clinical and pathological characteristics, treatments, and prognosis of gingival metastasis by HCC.

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Transcriptomic characterization of cancer-testis antigens identifies MAGEA3 as a driver of tumor progression in hepatocellular carcinoma

PLoS Genetics ◽

10.1371/journal.pgen.1009589 ◽

2021 ◽

Vol 17 (6) ◽

pp. e1009589

Author(s):

Amanda J. Craig ◽

Teresa Garcia-Lezana ◽

Marina Ruiz de Galarreta ◽

Carlos Villacorta-Martin ◽

Edgar G. Kozlova ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Progression ◽

Genetic Mouse Model ◽

Cancer Testis Antigens ◽

Poorly Differentiated ◽

Cancer Tissues ◽

Cancer Testis

Cancer testis antigens (CTAs) are an extensive gene family with a unique expression pattern restricted to germ cells, but aberrantly reactivated in cancer tissues. Studies indicate that the expression (or re-expression) of CTAs within the MAGE-A family is common in hepatocellular carcinoma (HCC). However, no systematic characterization has yet been reported. The aim of this study is to perform a comprehensive profile of CTA de-regulation in HCC and experimentally evaluate the role of MAGEA3 as a driver of HCC progression. The transcriptomic analysis of 44 multi-regionally sampled HCCs from 12 patients identified high intra-tumor heterogeneity of CTAs. In addition, a subset of CTAs was significantly overexpressed in histologically poorly differentiated regions. Further analysis of CTAs in larger patient cohorts revealed high CTA expression related to worse overall survival and several other markers of poor prognosis. Functional analysis of MAGEA3 was performed in human HCC cell lines by gene silencing and in a genetic mouse model by overexpression of MAGEA3 in the liver. Knockdown of MAGEA3 decreased cell proliferation, colony formation and increased apoptosis. MAGEA3 overexpression was associated with more aggressive tumors in vivo. In conclusion MAGEA3 enhances tumor progression and should be considered as a novel therapeutic target in HCC.

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