A new VETC in hepatocellular carcinoma metastasis

Hanley, Kaisa L.; Feng, Gen‐Sheng

doi:10.1002/hep.27860

Cited by 8 publications

(5 citation statements)

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“…Knockdown of Angpt2 in hepatoma cells abolishes VETC formation and, in turn, reduces the in vivo metastasis of HCC xenografts . These findings indicate VETC as a novel target for antimetastasis therapy, and highlight the need to identify the molecules that regulate the VETC pattern . However, the regulatory mechanisms of VETC formation in HCC remain unexplored.…”

Section: Introductionmentioning

confidence: 96%

MicroRNAs miR-125b and miR-100 suppress metastasis of hepatocellular carcinoma by disrupting the formation of vessels that encapsulate tumour clusters

et al. 2016

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We have previously shown that vessels that encapsulated tumour cluster (VETC), a prevalent vascular pattern in hepatocellular carcinoma (HCC), facilitates the entry of the whole tumour cluster into the bloodstream in an invasion-independent manner, and that angiopoietin 2 (Angpt2), the levels of which are increased in HCC cells, is essential for VETC formation. However, the mechanisms underlying VETC formation remains unclear. Herein, we characterized miR-125b and miR-100 as novel VETC suppressors by using human HCC specimens, and cell and animal models. We showed that reduced expression of either miR-125b or miR-100 in human HCC tissues was significantly associated with the presence of VETC, venous invasion of tumour cells, and the occurrence of endothelium-coated microemboli. To confirm the role of miR-125b and miR-100 in VETC formation and HCC metastasis, cell lines with stable miR-125b and miR-100 expression were established by using human VETC-2 cells and mouse Hepa1-6 cells, the hepatoma cells that developed xenografts with VETC patterns. Our results showed that expression of miR-125b or miR-100 in VETC-2 and Hepa1-6 cells dramatically reduced VETC formation in xenografts, and consequently inhibited in vivo metastasis, suggesting that miR-125b and miR-100 may attenuate metastasis by repressing VETC formation. Further investigation revealed that miR-125b directly suppressed the expression of Angpt2 by binding to its 3'-untranslated region, whereas miR-100 reduced the protein level of Angpt2 by targeting mechanistic target of rapamycin (MTOR) and blocking the MTOR-p70S6K signalling pathway. Moreover, the suppressive effect of miR-125b and miR-100 on VETC formation was abrogated by injecting Angpt2-expressing viruses into xenografts. Taken together, our findings imply that miR-125b and miR-100 negatively regulate Angpt2 expression through different mechanisms, in turn inhibit VETC formation, and consequently abrogate the VETC-dependent metastasis of hepatoma cells. This study uncovers new regulatory mechanisms of VETC formation, identifies novel functions of miR-125b and miR-100, and provides new targets for antimetastasis therapy of HCC. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Section: Introductionmentioning

confidence: 96%

MicroRNAs miR-125b and miR-100 suppress metastasis of hepatocellular carcinoma by disrupting the formation of vessels that encapsulate tumour clusters

et al. 2016

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“…Sorafenib (Nexavar ® ) and Lenvatinib (Lenvima ® ), two multi-kinase inhibitors with potent anti-angiogenic capacity, have been used as first-line therapies for hepatocellular carcinoma in the past [ 23 , 24 ]. The VETC pattern used has also been shown to be a predictive biomarker for sorafenib treatment efficacy [ 13 , 14 , 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…Angiogenesis is important for both tumor growth and metastases in HCC, and this can be identified using the intra-tumoral microvessel density (MVD) [ 11 , 12 ]. Vessels that encapsulate tumor clusters (VETC) are another specific tumor vascular pattern that has been reported recently [ 13 , 14 , 15 ]. Microscopically, each tumor cluster is encapsulated by sinusoid-like vessels that form cobweb-like networks [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

“…Microscopically, each tumor cluster is encapsulated by sinusoid-like vessels that form cobweb-like networks [ 16 ]. Knockdown of angiopoietin-2 (Ang2) could reduce the vascular pattern and decrease in vivo metastasis [ 13 ]. Fang and Xu et al reported that the VETC pattern in patients with HCC is a predictor of beneficial effects in sorafenib treatment, and that this may be related to its antagonistic effect on Ang2 [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

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The Vessels That Encapsulate Tumor Clusters (VETC) Pattern Is a Poor Prognosis Factor in Patients with Hepatocellular Carcinoma: An Analysis of Microvessel Density

Huang

Lin

Huang

et al. 2022

Cancers

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The outcomes of patients with hepatocellular carcinoma (HCC) are unsatisfactory because of its high recurrence rate. The Vessels that encapsulate tumor clusters (VETC) pattern is a unique vascular structure. In this study, we investigated the clinical–pathological features of HCC patients with the VETC pattern. We retrospectively reviewed patients with HCC who underwent curative hepatectomy at Chang Gung Memorial Hospital between 2007 and 2013. The form of the VETC pattern was established using an anti-CD31 stain. The results were classified into positive (VETC+) and negative (VETC−) patterns. We investigated and compared demographic data between these two groups. Overall, 174 patients were classified into either the VETC+ or VETC− groups. The median followed-up period was 80.5 months. There were significant differences in the number of hepatitis B carriers, the occurrence of vascular invasion, tumor size, TNM staging, microvessel density, and recurrence (all p < 0.05). Regarding the prediction of disease-free survival, after COX regression multivariate analysis, VETC+ remained independently associated with recurrent episodes (p = 0.003). The intra-tumoral microvessel density, demonstrated by CD-31, was the only clinical–pathological feature independently associated with VETC+. Our study demonstrated that the VETC pattern is an independent factor of poor prognosis for DFS. Higher intra-tumoral microvessel density was significantly associated with the VETC pattern. Further studies are needed to validate our findings.

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“…Surgical resection is still regarded as the first choice of HCC treatment [8][9][10][11][12] . However, due to intrahepatic metastasis and early recurrence, postoperative patients' prognosis is poor [13][14][15][16][17][18] , and the 5-year survival rate is relatively low [19] . The high recurrence and vascular invasion of HCC limit the long-term survival of HCC patients.…”

Section: Introductionmentioning

confidence: 99%

Advances in minimally invasive surgery for hepatocellular carcinoma

Zhang¹,

Li²

2020

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Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer-related death worldwide. Surgical resection is still regarded as the first choice of treatment for HCC. With advances in technology and techniques, minimally invasive surgery has now become the standard of care in almost every field in general surgery, including hepatectomy surgery. This review focuses on the latest advances in minimally invasive surgical treatment of HCC, including laparoscopic hepatectomy (LH), robotic hepatectomy (RH) and other minimally invasive treatment technologies. Although some limitation in LH or RH exists, these minimally invasive techniques may be performed for hepatectomy with benefits, and have a promising future. With the development of technology and the improvement of surgical operations, patients will benefit from this.

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A new VETC in hepatocellular carcinoma metastasis

Cited by 8 publications

References 9 publications

MicroRNAs miR-125b and miR-100 suppress metastasis of hepatocellular carcinoma by disrupting the formation of vessels that encapsulate tumour clusters

MicroRNAs miR-125b and miR-100 suppress metastasis of hepatocellular carcinoma by disrupting the formation of vessels that encapsulate tumour clusters

The Vessels That Encapsulate Tumor Clusters (VETC) Pattern Is a Poor Prognosis Factor in Patients with Hepatocellular Carcinoma: An Analysis of Microvessel Density

Advances in minimally invasive surgery for hepatocellular carcinoma

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