Role and mechanism of vasculogenic mimicry in gastrointestinal stromal tumors

Sun, Baocun; Qie, Shuo; Sun, Tao; Zhao, Xiulan; Gao, Songyuan; Ni, Chunsheng; Wang, Xinghui; Liu, Yanxue; Zhang, Lihua

doi:10.1016/j.humpath.2007.07.018

Cited by 76 publications

(59 citation statements)

References 20 publications

(25 reference statements)

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“…The presence of VM is closely associated with mitotic rate, histological subtype, Breslow thickness, ulceration, lymph node metastasis, and distant metastasis in melanoma. This result is consistent with earlier investigations (Sun et al 2008;Morselli et al 2009). In addition, we found that the presence of VM is reversely associated with melanin and tumor necrosis.…”

Section: Discussionsupporting

confidence: 94%

Overexpression of Microtubule-Associated Protein-1 Light Chain 3 Is Associated with Melanoma Metastasis and Vasculogenic Mimicry

Han

Sun

Wang

et al. 2011

Tohoku J. Exp. Med.

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Vasculogenic mimicry (VM) is an alternative type of blood supplement and is responsible for aggressive tumor biology and increased tumor-related mortality. Tumor cells obtain oxygen and nutriment through VM channels in the early, rapid-growth stage when blood vessels are insufficient. VM channels are characterized by tubular structures with tumor cells. Autophagy is a catabolic process, by which the cell digests damaged components or organelles of its own cytoplasm in response to nutrient deprivation, hypoxia, and the presence of non-functional protein aggregates. In fact, autophagy plays an important role in normal cell growth, development, and homeostasis. However, it is still controversial whether autophagy is also involved in cell death or cell survival in malignancy. In the present study, we therefore investigated the expression levels of two autophagy-related proteins, microtubule-associated protein-1 light chain 3 (LC3) and beclin-1, with respect to melanoma metastasis and vasculogenic mimicry. Melanoma is characterized by rapid growth, high-metastasis rate, and unpredictable behavior. A total of 70 human melanoma tissues were analyzed, showing that VM was present in 31 melanoma specimens (44.3%). Melanoma cells displayed high levels of autophagy when VM was present. Real-time quantitative PCR and immunohistochemical analyses showed that the expression levels of beclin-1 and LC3 mRNAs and proteins were both higher in the VM-positive melanoma than those in the VM-negative melanoma (p < 0.05). Moreover, the expression of LC3, rather than beclin-1, was strongly associated with metastasis and poor clinical prognosis of human melanoma. Therefore, the enhanced autophagic activity may be related to VM and metastasis of melanoma.Keywords: melanoma; vasculogenic mimicry; microtubule-associated protein 1 light chain 3; beclin-1; melanoma metastasis Tohoku J. Exp. Med., 2011, 223 (4), 243-251. © 2011 Tohoku University Medical Press Melanoma is characterized by poorly differentiated rapid growth, high-metastasis rate, and unpredictable behavior (McKinnon et al. 2003). It continues to be one of the most aggressive and fatal malignancies once metastasized. When distant metastasis occurs, the cancer is generally considered incurable. The five-year survival rate is less than 10%, whereas the median survival is 6-12 months (Balch et al. 2001). Accordingly, inhibiting metastasis can be an effective therapeutic strategy and benefit patients with melanoma. Despite many intensive laboratories and clinical researches, the mechanism involved in metastasis of melanoma still remains unclear.Some studies have confirmed that the presence of vasculogenic mimicry (VM) channels, a matrix-rich vascularlike network, and the development of fluid-conducting pathways by highly invasive and genetically dysregulated tumor cells are associated with more aggressive and metastatic tumor biology (Maniotis et al. 1999;Hess et al. 2001). VM has been described in highly metastatic malignant tumors, including melanoma (Folberg and Maniotis 2004), in...

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Section: Discussionsupporting

confidence: 94%

Overexpression of Microtubule-Associated Protein-1 Light Chain 3 Is Associated with Melanoma Metastasis and Vasculogenic Mimicry

Han

Sun

Wang

et al. 2011

Tohoku J. Exp. Med.

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“…These results indicate that VM promotes the likelihood of development, invasion and hematogenous metastases and is a worse prognostic factor of patients. Our study is consistent with previous researches (Shirakawa et al, 2002;Sun et al, 2004;Sun et al, 2008;Li et al, 2010;Zhang et al, 2013). We found that the positive-VM is formed by GAC cells with a much higher level in CD133-positive /Lgr5-positive cells, where high-density microvessels also observe.…”

Section: Discussionsupporting

confidence: 93%

Aberrant Expression of Markers of Cancer Stem Cells in Gastric Adenocarcinoma and their Relationship to Vasculogenic Mimicry

Zhou

Yu²,

Feng³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: Gastric cancer is the second leading cause of cancer-related death in Asia, and the majority type is gastric adenocarcinoma (GAC). Most GAC patients die of recurrence and metastasis. Cancer stem cells (CSCs) have been thought to be responsible for the initiation, development, metastasis, and ultimately recurrence of cancer. In this study, we aimed to investigate expression and clinical significance of CSCs markers, CD133 and Lgr5, and vasculogenic mimicry (VM) in primary GAC. Materials and Methods: Specimens from 261 Chinese patients with follow-up were analyzed for CD133, Lgr5 protein expression and VM by immunohistochemical and histochemical staining. The Pearson Chi's square test was used to assess the associations among the positive staining of these markers and clinicopathological characteristics. Postoperative overall survival time was were studied by univariate and multivariate analyses. Results: In GAC tissues, positive rates of 49.0%, 38.7%, and 26.8% were obtained for CD133, Lgr5, and VM, respectively. The mean score of microvessel density (MVD) was 21.7±11.1 in GAC tissues. There was a significantly difference between the positive and negative groups. There was a positive relationship between the VM, the expression of CD133 and Lgr5, and the score of MVD and the grades of tumor, lymph node metastasis, TNM stages (all p<0.05). The overall mean survival time of the patients with CD133, Lgr5, VM, and MVD (≥22) positive expression was lower than that of patients with negative expression. The score of MVD, positive expression of CD133 and VM were independent prognostic factors of GAC (p<0.05). Conclusions: VM, and expression of CD133, Lgr5, and the score of MVD are related to grades of tumor, lymph node metastasis, TNM stages, and overall mean survival time. It is suggested that CSCs and VM could play an important role in the evolution of GAC.

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“…Our data showed that the MVD of GBC samples was significantly higher in the non-VM group than that in the VM group. Work from several laboratories has revealed that VM was negatively correlated with MVD in several tumor types (17,41,45,46). Our results, together with the previous reports, indicated that VM could convey blood plasma and red blood cells to satisfy the growth of tumor and hematogenous metastasis independent of angiogenesis and revealed that the tumors with VM could remain non-necrotic due to the blood flow in VM and VM-angiogenesis junction although MVD was less.…”

Section: Discussionsupporting

confidence: 78%

Overexpression of HIF-1α in primary gallbladder carcinoma and its relation to vasculogenic mimicry and unfavourable prognosis

et al. 2012

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Abstract.As a novel mode of tumor neovascularization, vasculogenic mimicry (VM) has been reported to increase tumor-related mortality in many different solid tumors. In the present study, two established human gallbladder carcinoma (GBC) cell lines (highly aggressive GBC-SD and poorly aggressive SGC-996) cultured on a three-dimensional matrix were assessed for the ability of VM channel formation under normoxic or hypoxic conditions. In addition, the relationship between HIF-1α gene expression and VM channel formation of GBC cells in vitro was measured using the small interfering RNA (siRNA) technique, western blotting and real-time reverse transcription (RT)-PCR analysis. Furthermore, H&E and CD31/periodic acid-Schiff (PAS) staining were used to observe VM in GBC tissue samples. Additionally, all seventy-one specimens with VM and non-VM were stained for hypoxia inducible factor-1 α (HIF-1α) and its correlation with clinicopathological features and prognosis was analyzed simultaneously. We found that hypoxia could induce more VM channel formation and elevated HIF-1α expression in highly aggressive GBC-SD cells. HIF-1α siRNA efficiently knocked down HIF-1α expression and GBC VM networks under either normoxic or hypoxic conditions. VM was present in human primary GBC and overexpression of HIF-1α was significantly correlated with depth of invasion and perineural involvement in the non-VM group. Moreover, VM and HIF-1α were independent factors for the overall survival of GBC patients and correlated with decreased survival. In conclusion, VM was present in human GBC. As a critical mediator in VM formation, high expression of HIF-1α was associated with VM and tumor progression in GBC patients.

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Role and mechanism of vasculogenic mimicry in gastrointestinal stromal tumors

Cited by 76 publications

References 20 publications

Overexpression of Microtubule-Associated Protein-1 Light Chain 3 Is Associated with Melanoma Metastasis and Vasculogenic Mimicry

Overexpression of Microtubule-Associated Protein-1 Light Chain 3 Is Associated with Melanoma Metastasis and Vasculogenic Mimicry

Aberrant Expression of Markers of Cancer Stem Cells in Gastric Adenocarcinoma and their Relationship to Vasculogenic Mimicry

Overexpression of HIF-1α in primary gallbladder carcinoma and its relation to vasculogenic mimicry and unfavourable prognosis

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