Significance of autocrine mechanism of VEGF/VEGF receptor in ATL cell proliferation.

VEGF/VEGF受体自分泌机制在ATL细胞增殖中的意义。

基本信息

  • 批准号:
    13671069
  • 负责人:
  • 金额:
    $ 2.3万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    2001
  • 资助国家:
    日本
  • 起止时间:
    2001 至 2002
  • 项目状态:
    已结题

项目摘要

In the present study, in the co=culture system with MS-5, mouse-bone marrow derived stromal cells, MS-5, HTLV-I-transformed T cell lines and clinical samples of ATL cells grew in close contact with stromal layer and formed-so-called "cobblestone areas (CA)" composing 10 to over 100 cells. Morphology, immunophenotypirig, and southern blotting analysis indicated that CA-composing cells were compatible with ATL cells which were identical clone with primary ATL cells. Immunostaining and RNA, in situ hybridization indicated that viral protein, p40tax and p19gag was markedly decreased in CA cells in five cases. There was a linear relationship between inoculated cell number and CA numbers in seven ATL cases in semi-solid cultyure condition. Thus, our co-culture system provides for the first time the adhesion-dependent growth of primary ATL cells without production of HTLV-I-related proteins, which mimics in vivo growth of ATL cells. We detected Flt-1 mRNA and receptor expression in three ATL … More cell lines examined (KK1, SO4, and ST 1), whereas no KDR mRNA was detected. Concerning primary ATL cells from patients, expression of Flt-1 and KDR rRNA was seen in eight of 11 (73%) and one of 1l (9%) samples, respectively. Furthermore, mall three cell lines and 11 of 11 (100%) samples from ATL patients, expression of VEGF mRNA was detected. Anti-VEGF antibody, which could inhibit binding of VEGF and its receptors on ATL cells, had no significant effect on the cell proliferation of three ATL cell lines in liquid culture. Furthermore, the cell proliferation was not affected by recombinant human VEGF (rhVEGF) treatment (0-400 ng/ml) by MTT assay. On the other hand, in CA formation assay with our co-culture system, number of CA and cellular count of CA-composing cells were not affected compared with the condition of absence of anti-VEGF antibody. Furthermore, addition of rhVEGF had no effect of ATL-CA number or celluar count. Next, KKI was harvested from co-culture system after co-culturing at day 2,5, and 10 by trypsinization. As observed in CA formation assay, although harvested cellular numbers tended to be higher by addition of rhVEGF, there was no significant statistical difference between various condition. These observation indicated that VEGF has no significant effect on ATL cell growth in MS-5 co-culture system, for the present. The effect of VEGF/VEGF receptor-autocrine system, which is considered to be important on ATL cell biology in context of interaction with in vivo microenvironment, have to be elucidated more precisely, and further investigations are now in progress. Less
在本研究中,在与MS-5的共培养系统中,小鼠骨髓来源的基质细胞、MS-5、HTLV-1转化的T细胞系和ATL细胞的临床样品与基质层紧密接触生长,并形成由10至100多个细胞组成的所谓的“鹅卵石区域(CA)”。形态学、免疫表型和Southern印迹分析表明,CA合成细胞与ATL细胞相容,且与原代ATL细胞克隆完全相同。免疫组化和RNA原位杂交结果显示,5例CA细胞中病毒蛋白、p40 tax和p19 gag均明显减少。在半固体培养条件下,7例ATL的接种细胞数与CA数呈线性关系。因此,我们的共培养系统首次提供了原代ATL细胞的粘附依赖性生长,而不产生HTLV-I相关蛋白,这模拟了ATL细胞的体内生长。检测Flt-1 mRNA及其受体在三种ATL中的表达 ...更多信息 检测的细胞系(KK 1、SO 4和ST 1),而未检测到KDR mRNA。关于患者的原代ATL细胞,Flt-1和KDR rRNA的表达分别见于8/11(73%)和1/11(9%)样本。此外,在11例ATL患者的11例(100%)标本中,有11例(100%)检测到VEGFmRNA的表达。抗VEGF抗体可抑制ATL细胞表面VEGF及其受体的结合,但对ATL细胞的增殖无明显影响。MTT法检测重组人VEGF(rhVEGF)处理(0-400 ng/ml)对细胞增殖无明显影响。另一方面,在使用我们的共培养系统的CA形成测定中,与不存在抗VEGF抗体的条件相比,CA的数量和CA组成细胞的细胞计数不受影响。此外,添加rhVEGF对ATL-CA数量或细胞计数没有影响。然后,在共培养的第2、5和10天通过胰蛋白酶消化从共培养系统中收获KKI。如CA形成试验中所观察到的,虽然通过添加rhVEGF收获的细胞数倾向于更高,但是在各种条件之间没有显著的统计学差异。这些观察表明,目前VEGF对MS-5共培养体系中ATL细胞的生长没有明显影响。VEGF/VEGF受体-自分泌系统在与体内微环境相互作用的背景下对ATL细胞生物学的作用被认为是重要的,必须更精确地阐明,并且现在正在进行进一步的研究。少

项目成果

期刊论文数量(21)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Nagai K, Tsukasaki K, Tomonaga M. et al.: "Establishment of adhesion-dependent and clonal culture system of ATL cells without HTLV-1 expression."The 65^<th> Japanease Society of Hematology and the 45^<th> Japanease Society of Clinical Hematology. (2003)
Nagai K、Tsukasaki K、Tomonaga M.等人:“无HTLV-1表达的ATL细胞的粘附依赖性克隆培养系统的建立。”第65届日本血液学会和第45届日本血液学会
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    0
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Hayashibara T, Tomonaga M, et al.: "Vascular endothelial growth factor and cellular chemotaxis : a possible autocrine pathway in adult.T cell leukemia cell invasion."Clin Cancer Res. 7. 2716-2719 (2001)
Hayashibara T、Tomonaga M 等人:“血管内皮生长因子和细胞趋化性:成人中可能的自分泌途径。T 细胞白血病细胞侵袭。”临床癌症研究。
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    0
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Tsukasaki K, Nagai, Tomonaga M et al.: "Identifying progression-associated genes in adult T-cell leukemia/lymphoma by using oligonucleotide microarrays."ASH2O01..
Tsukasaki K、Nagai、Tomonaga M 等人:“通过使用寡核苷酸微阵列识别成人 T 细胞白血病/淋巴瘤中的进展相关基因。”ASH2O01..
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    0
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Mori N.et al.: "Human T-cell leukemia virus type I Tax transactivates the matrix metalloproteinase-9 gene : potential role in mediating adult T-cell leukemia invasiveness"BLOOD. 99・4. 1341-1349 (2002)
Mori N.等人:“人类T细胞白血病病毒I型Tax反式激活基质金属蛋白酶9基因:在介导成人T细胞白血病侵袭性中的潜在作用”BLOOD 1341-1349(2002)。
  • DOI:
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  • 影响因子:
    0
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Mori N., et al.: "Human T-cell leukemia virus type I Tax transactivates the matrix metalloproteinase-9 gene : potential role in mediating adult T-cell leukemia invasiveness."BLOOD. 99・4. 1341-1349 (2002)
Mori N., et al.:“人类 T 细胞白血病病毒 I 型 Tax 反式激活基质金属蛋白酶 9 基因:在介导成人 T 细胞白血病侵袭性中的潜在作用。”BLOOD 1341-1349 (2002)。
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    0
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TOMONAGA Masao其他文献

TOMONAGA Masao的其他文献

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{{ truncateString('TOMONAGA Masao', 18)}}的其他基金

Comparative study of refractory anemia(FAB)of MDS in clinical features between Japan and China Cooperative Group
中日MDS难治性贫血(FAB)临床特征比较研究
  • 批准号:
    18406033
  • 财政年份:
    2006
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Development of a new classification for AML based on the gene expression profile in leukemia stem cells.
根据白血病干细胞的基因表达谱开发新的 AML 分类。
  • 批准号:
    15390303
  • 财政年份:
    2003
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Analysis of proviral and cellular genome abnormalities found during disease progression in adult T-cell leukemia/lymphoma
分析成人 T 细胞白血病/淋巴瘤疾病进展过程中发现的前病毒和细胞基因组异常
  • 批准号:
    09671122
  • 财政年份:
    1997
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
ANALYSES OF GENOMIC IMPRINTING IN CHROMOSOME TRANSLOCATIONS OF HEMATOLOGIC NEOPLASIA
血液肿瘤染色体易位基因组印记分析
  • 批准号:
    06671100
  • 财政年份:
    1994
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

相似海外基金

Vascular endotherial growth factor )VEGF) in paranasal sinusitis and allergic rhinitis
血管内皮生长因子 (VEGF) 在鼻窦炎和过敏性鼻炎中的作用
  • 批准号:
    11671694
  • 财政年份:
    1999
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
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