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从BKV/tat转基因小鼠的卡波西肉瘤样病变中分离出的梭形细胞共表达不同细胞类型的标志物。

Spindle cells isolated from Kaposi's sarcoma-like lesions of BKV/tat-transgenic mice co-express markers of different cell types.

作者信息

Cavallaro U, Gasparini G, Soria M R, Maier J A

机构信息

Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan, Italy.

出版信息

AIDS. 1996 Sep;10(11):1211-9. doi: 10.1097/00002030-199609000-00006.

DOI:10.1097/00002030-199609000-00006
PMID:8883582
Abstract

OBJECTIVE

To characterize murine spindle cells isolated from Kaposi's sarcoma-like skin lesions developed in BK virus (BKV)/tat-transgenic mice.

METHODS

Kaposi's sarcoma-like spindle cells isolated from the lesions were propagated in vitro, and their phenotype was investigated using a panel of antibodies against various cell markers and angiogenic factors. Immunofluorescence and Western blot techniques were used.

RESULTS

We observed co-expression of antigens specific for endothelial, smooth muscle and antigen-presenting cells, suggesting that cells from the TTB cell line represent poorly differentiated vascular precursors. Since TTB cells were derived from highly vascularized skin lesions, it is noteworthy that they synthesize a complex mixture of angiogenic factors, including fibroblast growth factor-2, vascular endothelial growth factor, placental growth factor, and hepatocyte growth factor. Due to their role in invasiveness and angiogenesis, we also observed the expression of urokinase plasminogen activator (uPA), uPA receptor, and plasminogen activator inhibitor-type 1 by TTB cells.

CONCLUSIONS

Our results suggest that TTB cells share several features with human Kaposi's sarcoma spindle cells and can be a useful in vitro system to study the molecular mechanisms involved in Kaposi's sarcoma pathogenesis. Moreover, they synthesize a complex mixture of angiogenic factors and are growth-inhibited by the anti-angiogenic drug AGM-1470.

摘要

目的

对从BK病毒(BKV)/tat转基因小鼠发生的卡波西肉瘤样皮肤病变中分离出的小鼠纺锤体细胞进行表征。

方法

从病变中分离出的卡波西肉瘤样纺锤体细胞在体外进行增殖,使用一组针对各种细胞标志物和血管生成因子的抗体研究其表型。采用免疫荧光和蛋白质印迹技术。

结果

我们观察到内皮细胞、平滑肌细胞和抗原呈递细胞特异性抗原的共表达,这表明TTB细胞系的细胞代表分化程度低的血管前体细胞。由于TTB细胞来源于高度血管化的皮肤病变,值得注意的是它们合成了包括成纤维细胞生长因子-2、血管内皮生长因子、胎盘生长因子和肝细胞生长因子在内的复杂血管生成因子混合物。由于它们在侵袭和血管生成中的作用,我们还观察到TTB细胞表达尿激酶型纤溶酶原激活剂(uPA)、uPA受体和1型纤溶酶原激活剂抑制剂。

结论

我们的结果表明,TTB细胞与人类卡波西肉瘤纺锤体细胞具有若干共同特征,可作为研究卡波西肉瘤发病机制所涉及分子机制的有用体外系统。此外,它们合成复杂的血管生成因子混合物,并被抗血管生成药物AGM-1470抑制生长。

相似文献

1
Spindle cells isolated from Kaposi's sarcoma-like lesions of BKV/tat-transgenic mice co-express markers of different cell types.从BKV/tat转基因小鼠的卡波西肉瘤样病变中分离出的梭形细胞共表达不同细胞类型的标志物。
AIDS. 1996 Sep;10(11):1211-9. doi: 10.1097/00002030-199609000-00006.
2
FGF-2 stimulates migration of Kaposi's sarcoma-like vascular cells by HGF-dependent relocalization of the urokinase receptor.成纤维细胞生长因子-2通过尿激酶受体的肝细胞生长因子依赖性重新定位刺激卡波西肉瘤样血管细胞迁移。
FASEB J. 1998 Aug;12(11):1027-34. doi: 10.1096/fasebj.12.11.1027.
3
The urokinase-type plasminogen activator, its receptor and u-PA inhibitor type-1 affect in vitro growth and invasion of Kaposi's sarcoma and capillary endothelial cells: role of HIV-Tat protein.尿激酶型纤溶酶原激活剂、其受体及1型尿激酶型纤溶酶原激活剂抑制剂对卡波西肉瘤和毛细血管内皮细胞体外生长及侵袭的影响:HIV-Tat蛋白的作用
Int J Oncol. 2005 Jul;27(1):223-35.
4
Differential response to Tat and FGF-2 of two novel clonal populations derived from murine Kaposi-like lesions developing in Tat transgenic mice.源自Tat转基因小鼠中发生的卡波西样病变的两个新克隆群体对Tat和FGF-2的差异反应。
Microvasc Res. 2002 Jan;63(1):19-26. doi: 10.1006/mvre.2001.2361.
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Characterization of a human Kaposi's sarcoma cell line that induces angiogenic tumors in animals.
AIDS. 1994 May;8(5):575-81. doi: 10.1097/00002030-199405000-00002.
6
Interleukin 1 induces an autocrine loop hepatocyte growth factor/c-Met in murine Kaposi-like spindle cells.白细胞介素1在小鼠卡波西样梭形细胞中诱导肝细胞生长因子/c-Met自分泌环路。
Oncogene. 1996 Sep 5;13(5):1009-15.
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Exogenous fibroblast growth factor-2 induces a transformed phenotype in vascular kaposi's sarcoma-like cells.外源性成纤维细胞生长因子-2可诱导血管卡波西肉瘤样细胞出现转化表型。
Mol Cell Biol Res Commun. 2000 Oct;4(4):203-5. doi: 10.1006/mcbr.2001.0278.
8
Angiogenic potential in vivo by Kaposi's sarcoma cell-free supernatants and HIV-1 tat product: inhibition of KS-like lesions by tissue inhibitor of metalloproteinase-2.卡波西肉瘤无细胞上清液和HIV-1 tat产物在体内的血管生成潜力:金属蛋白酶组织抑制剂-2对卡波西肉瘤样病变的抑制作用
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G-protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus is a viral oncogene and angiogenesis activator.卡波西肉瘤相关疱疹病毒的G蛋白偶联受体是一种病毒癌基因和血管生成激活剂。
Nature. 1998 Jan 1;391(6662):86-9. doi: 10.1038/34193.
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Inflammatory cytokines synergize with the HIV-1 Tat protein to promote angiogenesis and Kaposi's sarcoma via induction of basic fibroblast growth factor and the alpha v beta 3 integrin.炎症细胞因子与HIV-1 Tat蛋白协同作用,通过诱导碱性成纤维细胞生长因子和αvβ3整合素来促进血管生成和卡波西肉瘤。
J Immunol. 1999 Aug 15;163(4):1929-35.

引用本文的文献

1
Kaposi's Sarcoma Lesion Progression in BKV-Tat Transgenic Mice Is Increased by Inflammatory Cytokines and Blocked by Treatment with Anti-Tat Antibodies.炎症细胞因子可促进BKV-Tat转基因小鼠卡波西肉瘤病变进展,而抗Tat抗体治疗可抑制其进展。
Int J Mol Sci. 2022 Feb 14;23(4):2081. doi: 10.3390/ijms23042081.
2
Characterization of novel clonal murine endothelial cell lines with an extended life span.具有延长寿命的新型克隆小鼠内皮细胞系的特性分析。
In Vitro Cell Dev Biol Anim. 2000 May;36(5):299-308. doi: 10.1290/1071-2690(2000)036<0299:CONCME>2.0.CO;2.
3
Fibronectin modulates the effects of HIV-1 Tat on the growth of murine Kaposi's sarcoma-like cells through the down-regulation of tyrosine phosphorylation.
纤连蛋白通过下调酪氨酸磷酸化来调节HIV-1反式激活因子对小鼠卡波西肉瘤样细胞生长的影响。
Am J Pathol. 1998 Jun;152(6):1599-605.