Human epidermal growth factor receptor signaling contributes to tumor growth via angiogenesis in her2/neu-expressing experimental Wilms' tumor.
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.
Yokoi
Akiko
A
Division of Pediatric Surgery, Columbia University, New York, NY, USA.
McCrudden
Kimberly W
KW
Huang
Jianzhong
J
Kim
Eugene S
ES
Soffer
Samuel Z
SZ
Frischer
Jason S
JS
Serur
Anna
A
New
Tamara
T
Yuan
Jenny
J
Mansukhani
Mahesh
M
O'toole
Kathleen
K
Yamashiro
Darrell J
DJ
Kandel
Jessica J
JJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000378:metabolism / Q000637:transplantation; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D007680:Kidney Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000172:deficiency / Q000276:immunology / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000503:physiopathology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000172:deficiency / Q000276:immunology / Q000502:physiology*; D000068878:Trastuzumab; D009396:Wilms Tumor / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab