Human epidermal growth factor receptor signaling contributes to tumor growth via angiogenesis in her2/neu-expressing experimental Wilms' tumor

J Pediatr Surg. 2003 Nov;38(11):1569-73. doi: 10.1016/s0022-3468(03)00562-1.

Abstract

Background: The human epidermal growth factor family (HER) members play a significant role in the mesenchymal-to-epithelial transition during renal tubulogenesis. HER misexpression has been linked also to loss of growth control, invasiveness, and promotion of angiogenesis in breast cancers and other human malignant tumors

Methods: The authors screened Wilms' tumor samples and derived cell lines for expression of her2/neu, which was detected in both unfavorable and favorable histology tissues. Xenografts were implanted in mice using her2/neu(+) and her2/neu(-) cell lines and the effect of specific blockade tested using monoclonal anti-her2/neu antibody.

Results: Blocking antibody suppressed tumor growth in her2/neu(+) but not her2/neu(-) experimental Wilms' tumor. In addition, antibody exposure resulted in suppression of tumor angiogenesis but no decrease in tumor cell proliferation in her2/neu(+) xenografts.

Conclusions: Her2/neu contributes to the growth of some Wilms' tumors, and an important mechanism of its action is promotion of angiogenesis.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Cell Division / drug effects
  • Cell Line, Tumor / metabolism
  • Cell Line, Tumor / transplantation
  • Female
  • Genes, erbB-2
  • Humans
  • Kidney Neoplasms / blood supply*
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / therapy
  • Mice
  • Mice, Nude
  • Neoplasm Proteins / deficiency
  • Neoplasm Proteins / immunology
  • Neoplasm Proteins / physiology*
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / physiopathology*
  • Receptor, ErbB-2 / deficiency
  • Receptor, ErbB-2 / immunology
  • Receptor, ErbB-2 / physiology*
  • Trastuzumab
  • Wilms Tumor / blood supply*
  • Wilms Tumor / genetics
  • Wilms Tumor / metabolism
  • Wilms Tumor / therapy
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Neoplasm Proteins
  • Receptor, ErbB-2
  • Trastuzumab