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首页> 外文学位 >The contribution of vascular endothelial growth factor-induced angiogenesis to the progression of primary human melanoma.
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The contribution of vascular endothelial growth factor-induced angiogenesis to the progression of primary human melanoma.

机译：血管内皮生长因子诱导的血管生成对原发性人类黑素瘤进展的贡献。

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摘要

Early stage primary human melanomas are known to remain relatively avascular and dormant for up to a decade or longer after which they may give rise to more rapidly growing, vascular and metastatically-competent primary tumors. The clinical behavior of melanoma recapitulated experimentally by injection of cell lines established from such tumors into nude mice. WM1341B cells, which were isolated from early stage human melanoma, are non-tumorigenic and display a dormant phenotype in nude mice. These cells produce little or no vascular endothelial growth factor (VEGF), a potent stimulator of angiogenesis, in culture. In order to determine whether their in vivo dormant behavior may be related to an inability to induce tumor angiogenesis, subpopulations of WM1341B cells were engineered to constitutively overexpress the VEGF{dollar}sb{lcub}121{rcub}{dollar} isoform. This modification was sufficient to induce overtly progressively growing tumors by several independent VEGF{dollar}sb{lcub}121{rcub}{dollar} producing clones and could be strongly suppressed by treatment of mice with a monoclonal anti-VEGF neutralizing (A4.6.1) antibody. These results support the notion that defective angiogenesis may, in part, account for the dormant phenotype of early stage primary melanoma lesions. Furthermore, this system may be useful as a tool to screen new anti-angiogenic agents for cancer therapy.
机译：已知早期人类原发性黑色素瘤在长达十年或更长时间内仍保持相对无血管和休眠状态，此后它们可能引起生长更快，具有血管和转移能力的原发性肿瘤。通过将由此类肿瘤建立的细胞系注射到裸鼠中，实验性地总结了黑色素瘤的临床行为。从早期人类黑色素瘤中分离出来的WM1341B细胞是非致瘤性的，在裸鼠中表现出休眠表型。这些细胞在培养中几乎不产生或不产生血管内皮生长因子（VEGF），即血管生成的有效刺激剂。为了确定它们的体内休眠行为是否可能与无法诱导肿瘤血管生成有关，对WM1341B细胞亚群进行了工程改造，使其组成型过表达VEGF {slb {lcub} 121 {rcub} {dollar}亚型。此修饰足以诱导几个独立的VEGF产生的克隆明显促进肿瘤的逐步生长，并且可以通过用单克隆抗VEGF中和剂治疗小鼠而被强烈抑制（A4.6.1 ）抗体。这些结果支持这样的观点，即血管新生缺陷可能部分解释了早期原发性黑色素瘤病变的休眠表型。此外，该系统可用作筛选用于癌症治疗的新抗血管生成剂的工具。

著录项

  • 作者

    Bayko, Liisa Ann.;

  • 作者单位

    University of Toronto (Canada).;

  • 授予单位 University of Toronto (Canada).;
  • 学科 Biophysics Medical.; Health Sciences Oncology.; Biology Cell.
  • 学位 M.Sc.
  • 年度 1997
  • 页码 96 p.
  • 总页数 96
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物物理学;肿瘤学;细胞生物学;
  • 关键词

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