Establishment of a novel experimental model of human angiosarcoma and a VEGF-targeting therapeutic experiment

Hoshina, Daichi; Abe, Riichiro; Yoshioka, Naoya; Saito, Nagahito; Hata, Hiroo; Fujita, Yasuyuki; Aoyagi, Satoka; Shimizu, Hiroshi

doi:10.1016/j.jdermsci.2013.02.008

Cited by 26 publications

(31 citation statements)

References 29 publications

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“…We used four human cutaneous angiosarcoma cell lines, HAMON (passage 8–20), ISO‐HAS (passage > 300), MO‐LAS (passage > 300) and ISOS‐1 (passage > 300) . HAMON was kindly donated by Daichi Hoshina and Riichiro Abe.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of heat shock protein 90 exerts an antitumour effect in angiosarcoma: involvement of the vascular endothelial growth factor signalling pathway

et al. 2017

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Section: Methodsmentioning

confidence: 99%

Inhibition of heat shock protein 90 exerts an antitumour effect in angiosarcoma: involvement of the vascular endothelial growth factor signalling pathway

et al. 2017

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“…They were cultured as previously described, [34][35][36] and were used in fewer than 6 mo of continuous passage. The cell lines were incubated with or without 10 ng/mL or 100 ng/mL recombinant human IFNg (R&D) for 24 h before analysis.…”

Section: Cell Linementioning

confidence: 99%

Infiltration of PD-1-positive cells in combination with tumor site PD-L1 expression is a positive prognostic factor in cutaneous angiosarcoma

et al. 2016

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Cutaneous angiosarcoma (CAS) is a malignant sarcoma with poor prognosis. Programmed cell death-1 (PD-1)/programmed cell death-1 ligand-1 (PD-L1) expression reflects antitumor immunity, and is associated with patient prognosis in various cancers. The purpose of this study is to investigate the relationship between PD-1/PD-L1 expression and CAS prognosis. CAS cases (n D 106) were immunohistochemically studied for PD-L1 and PD-1 expression, and the correlation with patient prognosis was analyzed. PD-L1 expression was assessed by flow cytometry on three CAS cell lines with or without IFNg stimulation. A total of 30.2% of patients' samples were positive for PD-L1, and 17.9% showed a high infiltration of PD-1-positive cells. Univariate analysis showed a significant relationship between a high infiltration of PD-1-positive cells with tumor site PD-L1 expression and favorable survival in stage 1 patients (p D 0.014, log-rank test). Multivariable Cox-proportional hazard regression analysis also showed that patients with a high infiltration of PD-1-positive cells with tumor site PD-L1 expression were more likely to have favorable survival, after adjustment with possible confounders (hazard ratio (HR) D 0.38, p D 0.021, 95% confidence interval (CI) 0.16-0.86). Immunofluorescence staining of CAS samples revealed that PD-L1-positive cells were adjacent to PD-1-positive cells and/or tumor stroma with high IFNg expression. In vitro stimulation with IFNg increased PD-L1 expression in two out of three established CAS cell lines. Our results suggest that PD-1/PD-L1 expression is related to CAS progression, and the treatment with anti-PD-1 antibodies could be a new therapeutic option for CAS.

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“…Two reported AS models in the literature are based on AS cell implantation into immunodeficient mice. 33,34 One drawback of our Notch1 KO mouse model to study AS biology and treatment strategies is the fact that the time point of tumor occurrence is not predictable and varies from animal to animal. Using our generated AS cell lines, we have established a tumor implantation model leading to subcutaneous AS formation, allowing visual control of tumor development and providing an attractive model to determine the in vivo efficacy of anticancer drugs.…”

Section: Discussionmentioning

confidence: 99%

Generation of a murine hepatic angiosarcoma cell line and reproducible mouse tumor model

Rothweiler¹,

Dill²,

Terracciano

et al. 2015

Laboratory Investigation

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Hepatic angiosarcoma (AS) is a rare and highly aggressive tumor of endothelial origin with dismal prognosis. Studies of the molecular biology of AS and treatment options are limited as animal models are rare. We have previously shown that inducible knockout of Notch1 in mice leads to spontaneous formation of hepatic AS. The aims of this study were to: (1) establish and characterize a cell line derived from this murine AS, (2) identify molecular pathways involved in the pathogenesis and potential therapeutic targets, and (3) generate a tumor transplantation model. AS cells retained specific endothelial properties such as tube formation activity, as well as expression of CD31 and Von Willebrand factor. However, electron microscopy analysis revealed signs of dedifferentiation with loss of fenestrae and loss of contact inhibition. Microarray and pathway analysis showed substantial changes in gene expression and revealed activation of the Myc pathway. Exposing the AS cells to sorafenib reduced migration, filopodia dynamics, and cell proliferation but did not induce apoptosis. In addition, sorafenib suppressed ERK phosphorylation and expression of cyclin D2. Injection of AS cells into NOD/SCID mice resulted in formation of undifferentiated tumors, confirming the tumorigenic potential of these cells. In summary, we established and characterized a murine model of spontaneous AS formation and hepatic AS cell lines as a useful in vitro tool. Our data demonstrate antitumor activity of sorafenib in AS cells with potent inhibition of migration, filopodia formation, and cell proliferation, supporting further evaluation of sorafenib as a novel treatment strategy. In addition, AS cell transplantation provides a subcutaneous tumor model useful for in vivo preclinical drug testing.

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Establishment of a novel experimental model of human angiosarcoma and a VEGF-targeting therapeutic experiment

Cited by 26 publications

References 29 publications

Inhibition of heat shock protein 90 exerts an antitumour effect in angiosarcoma: involvement of the vascular endothelial growth factor signalling pathway

Inhibition of heat shock protein 90 exerts an antitumour effect in angiosarcoma: involvement of the vascular endothelial growth factor signalling pathway

Infiltration of PD-1-positive cells in combination with tumor site PD-L1 expression is a positive prognostic factor in cutaneous angiosarcoma

Generation of a murine hepatic angiosarcoma cell line and reproducible mouse tumor model

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