Signalling pathways in vasculogenic mimicry

Paulis, Yvette W.J.; Soetekouw, Patricia M.M.B.; Verheul, Henk M.W.; Tjan‐Heijnen, Vivianne C. G.; Griffioen, Arjan W.

doi:10.1016/j.bbcan.2010.01.001

Cited by 132 publications

(162 citation statements)

References 117 publications

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“…In human solid tumors, lack of angiogenesis is a very rare event and was initially reported in melanomas and occasionally in other non-melanoma cancers including breast, ovarian, prostate, and renal clear cell carcinomas. 16 Blood circulation was established in those tumors by creating vascular channels lined by tumor cells, and this process has been termed as 'vasculogenic mimicry', which underscores the de novo generation of vascular channels without involvement of non-neoplastic endothelial cells. 17,18 With vasculogenic mimicry, it is thought that tumor cells are able to sustain tumor growth and, to some extent, prevent tumor hypoxia.…”

Section: Discussionmentioning

confidence: 99%

Trophoblastic vasculogenic mimicry in gestational choriocarcinoma

Shih

2011

Modern Pathology

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Angiogenesis is a characteristic feature of solid tumors, which depend on the newly formed vasculature to prevent hypoxia and to sustain uncontrolled tumor cell proliferation. In this study, we investigated the blood supply system in 10 gestational choriocarcinomas on the basis of histopathological and immunohistochemical features. In all examined cases, morphological analysis demonstrated that blood channels within the center of choriocarcinomas were surrounded by neoplastic trophoblastic cells rather than by endothelial cells. Similarly, there was a lack of CD31 and CD34-positive endothelial cells within choriocarcinomas. In the periphery of choriocarcinomas, tumor cells invaded uterine stroma-derived blood vessels where trophoblastic cells replaced endothelial cells, forming anastomoses between endothelium-lined blood vessels and trophoblastlined pseudovascular channels. Masson's trichrome staining revealed minimal amounts of connective tissue within choriocarcinomas. In contrast, CD31 and CD34-positive blood vessels were present in other types of gestational trophoblastic neoplasms including 8 placental site trophoblastic tumors and 12 epithelioid trophoblastic tumors. These findings provide cogent evidence that choriocarcinoma represents one of a few human tumor types that utilizes vasculogenic mimicry by tumor cell in supporting tumor development.

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Section: Discussionmentioning

confidence: 99%

Trophoblastic vasculogenic mimicry in gestational choriocarcinoma

Shih

2011

Modern Pathology

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“…There are two important features of aggressive glioma cells capable of VM formation: first, these cells exhibit a remarkable degree of plasticity, and second, these cells lost expression of some tumor cell markers but have a multipotent phenotype usually associated with embryonic stem cells and endothelial progenitor cells (Seftor et al 2012). The functional plasticity and multipotent phenotype associated with VM are supported by a complex combination of signaling pathways, of which the hypoxia-related signaling cascade plays a key regulatory role (Paulis et al 2010). Hypoxic culturing is able to induce VM formation in several highly aggressive human glioma cell lines (Huang et al 2014).…”

Section: Discussionmentioning

confidence: 99%

“…VM is the formation of a fluid-conducting network characterized by vascular channels that are exclusively lined by tumor cells mimicking endothelial cells (Misra et al 2012). This process is different from classic vasculogenesis by endothelial cells because of the lack of an endothelial monolayer, but it has a function in sustaining tumor microcirculation (Paulis et al 2010). Previous studies have found that VM formation is closely associated with development of malignant gliomas (Wang et al 2013;Wang et al 2012), and yet, the mechanisms involved in the regulation of VM process in glioma cells still remain elusive.…”

Section: Introductionmentioning

confidence: 99%

LRIG1 inhibits hypoxia-induced vasculogenic mimicry formation via suppression of the EGFR/PI3K/AKT pathway and epithelial-to-mesenchymal transition in human glioma SHG-44 cells

Zhang

Song

Wei

et al. 2015

Cell Stress and Chaperones

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Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a pan-negative regulator of the epidermal growth factor receptor (EGFR) signaling pathway. The aim of this study was to investigate the underlying mechanism of LRIG1 in the regulation of vasculogenic mimicry (VM) formation in glioma cells. We constructed an enhanced green fluorescent protein plasmid (pEGFP) system, pEGFP-C1-LRIG1, for overexpression of LRIG1, and transfected it into human glioma cell line SHG-44. Under hypoxic conditions induced by CoCl 2 , we investigated the effects of LRIG1 overexpression on VM formation and VM-dependent malignant behaviors including migration, invasion, and proliferation. Additionally, we explored the effects of LRIG1 on the expression levels of major components of the EGFR/PI3K/AKT pathway as well as E-cadherin and vimentin. We found that LRIG1 overexpression is able to inhibit hypoxia-induced VM formation, migration, invasion, and proliferation. Furthermore, LRIG1 overexpression counteracts hypoxiainduced increase in the expression of phosphorylated EGFR (pEGFR), PI3K (pPI3K), and AKT (pAKT) and reverts hypoxia-induced alteration in E-cadherin and vimentin expression levels. In LRIG1 knockdown SHG-44 cells, however, hypoxia-induced VM formation and alteration in E-cadherin and vimentin expression levels were exacerbated. These results suggest that the inhibitory effects of LRIG1 are most likely mediated by suppression of the EGFR/PI3K/AKT pathway and epithelial-mesenchymal transition (EMT) process. Our findings provide compelling evidence implicating LRIG1 in glioma pathophysiology, suggesting that gene therapy using LRIG1 may serve as a treatment for this disease.

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“…Indeed, a number of data in the literature indicate that avb5 integrin can be regulated by protein kinases: (i) several avb5 integrin-mediated functions (such as cell spreading, colocalization of a-actinin, tensin, vinculin, p130Cas, actin and induction of FAK tyrosine phosphorylation) require PKC activation 42 ; (ii) the cross-talk between avb5 integrin and the epidermal growth factor receptor, implicated in the metastatic process of pancreatic carcinoma cells, involves signalling kinases such as Src and Rap-1 43 (iii) the role played by avb5 integrin in the vasculogenic mimicry of melanoma cells 27 is under the control of kinases, such as PKC, Akt, FAK or ERK. 44,45 Interestingly, NRP-1 expression in melanoma cells promotes an increased secretion of MMP-2. 16 Since, it has been demonstrated that MMP-2 induces the activation of avb5 integrin, 30 this mechanism might also account for avb5 integrin triggering in NRP-1 positive melanoma cells.…”

Section: Discussionmentioning

confidence: 99%

Cilengitide downmodulates invasiveness and vasculogenic mimicry of neuropilin 1 expressing melanoma cells through the inhibition of αvβ5 integrin

Ruffini

Graziani

Levati

et al. 2014

Intl Journal of Cancer

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During melanoma progression, tumour cells show increased adhesiveness to the vascular wall, invade the extracellular matrix (ECM) and frequently form functional channels similar to vascular vessels (vasculogenic mimicry). These properties are mainly mediated by the interaction of integrins with ECM components. Since we had previously identified neuropilin 1 (NRP-1), a coreceptor of vascular endothelial growth factor A (VEGF-A), as an important determinant of melanoma aggressiveness, aims of this study were to identify the specific integrins involved in the highly invasive phenotype of NRP-1 expressing cells and to investigate their role as targets to counteract melanoma progression. Melanoma aggressiveness was evaluated in vitro as cell ability to migrate through an ECM layer and to form tubule-like structures using transfected cells. Integrins relevant to these processes were identified using specific blocking antibodies. The avb5 integrin was found to be responsible for about 80% of the capability of NRP-1 expressing cells to adhere on vitronectin. In these cells avb5 expression level was twice higher than in low-invasive control cells and contributed to the ability of melanoma cells to form tubule-like structures on matrigel. Cilengitide, a potent inhibitor of am integrins activation, reduced ECM invasion, vasculogenic mimicry and secretion of VEGF-A and metalloproteinase 9 by melanoma cells. In conclusion, we demonstrated that amb5 integrin is involved in the highly aggressive phenotype of melanoma cells expressing NRP-1. Moreover, we identified a novel mechanism that contributes to the antimelanoma activity of the av integrin inhibitor cilengitide based on the inhibition of vasculogenic mimicry.

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Signalling pathways in vasculogenic mimicry

Cited by 132 publications

References 117 publications

Trophoblastic vasculogenic mimicry in gestational choriocarcinoma

Trophoblastic vasculogenic mimicry in gestational choriocarcinoma

LRIG1 inhibits hypoxia-induced vasculogenic mimicry formation via suppression of the EGFR/PI3K/AKT pathway and epithelial-to-mesenchymal transition in human glioma SHG-44 cells

Cilengitide downmodulates invasiveness and vasculogenic mimicry of neuropilin 1 expressing melanoma cells through the inhibition of αvβ5 integrin

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