Establishment of a new murine-phenotypic angiosarcoma cell line (ISOS-1)

Masuzawa, Mikio; Fujimura, Takao; Tsubokawa, Mikihiko; Nishiyama, Shigeo; Katsuoka, Kensei; Terada, Eiji; Kunita, Satoshi; Sakurai, Yoshinori; Kato, Hideki

doi:10.1016/s0923-1811(97)00032-7

Cited by 33 publications

(31 citation statements)

References 26 publications

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“…One of the challenges facing mechanistic studies on angiosarcomas at the cellular level is that these tumors are composed of multiple cell populations that are prone to the loss of some endothelial markers upon in vitro culturing. 35,36 Therefore, establishing a primary murine angiosarcoma cell line that can give rise to secondary tumors in allotransplantation assays has been proven difficult. 6,7 Using our mouse model, we experienced similar difficulties in establishing a hemangiosarcoma cell line that would reliably reflect this disease in vitro.…”

Section: Discussionmentioning

confidence: 99%

Loss of autocrine endothelial-derived VEGF significantly reduces hemangiosarcoma development in conditional p53-deficient mice

et al. 2014

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Malignant transformation of the endothelium is rare, and hemangiosarcomas comprise only 1% of all sarcomas. For this reason and due to the lack of appropriate mouse models, the genetic mechanisms of malignant endothelial transformation are poorly understood. Here, we describe a hemangiosarcoma mouse model generated by deleting p53 specifically in the endothelial and hematopoietic lineages. This strategy led to a high incidence of hemangiosarcoma, with an average latency of 25 weeks. To study the in vivo roles of autocrine or endothelial cell autonomous VEGF signaling in the initiation and/or progression of hemangiosarcomas, we genetically deleted autocrine endothelial sources of VEGF in this mouse model. We found that loss of even a single conditional VEGF allele results in substantial rescue from endothelial cell transformation. These findings highlight the important role of threshold levels of autocrine VEGF signaling in endothelial malignancies and suggest a new approach for hemangiosarcoma treatment using targeted autocrine VEGF inhibition

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Section: Discussionmentioning

confidence: 99%

Loss of autocrine endothelial-derived VEGF significantly reduces hemangiosarcoma development in conditional p53-deficient mice

et al. 2014

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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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“…27,28 The AS cell line ISOS-1 was established from human scalp AS transplanted into immunodeficient mice. 29 Furthermore, a total of seven canine AS cell lines were established from three different xenograft canine tumors. 30 Although there are a number of AS cell lines derived from cutaneous tumors, so far only one cell line has been generated from hepatic AS.…”

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 new murine-phenotypic angiosarcoma cell line (ISOS-1)

Cited by 33 publications

References 26 publications

Loss of autocrine endothelial-derived VEGF significantly reduces hemangiosarcoma development in conditional p53-deficient mice

Loss of autocrine endothelial-derived VEGF significantly reduces hemangiosarcoma development in conditional p53-deficient mice

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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