VEGF-DT385 toxin conjugate inhibits mammary adenocarcinoma development in a transgenic mouse model of spontaneous tumorigenesis

R. Wild, Y. Yokoyama, R. P.M. Dings, Sundaram Ramakrishnan

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Previous experiments have shown that a vascular endothelial growth factor (VEGF)-DT385 toxin conjugate inhibits endothelial cell proliferation, angiogenesis and solid tumor growth in a xenotransplant model system. Here, we report that VEGF-DT385 toxin conjugate effectively inhibits spontaneous tumorigenesis. The C3(1)/SV40 TAg transgenic mouse model of mammary gland carcinogenesis was used to determine the effectiveness of VEGF-DT385 toxin conjugate in delaying the onset of disease and the development of solid tumors. Animals were treated daily with conjugate for a period of 7 days. Therapy was initiated at week 14 of development before any visible adenocarcinomas were evident. Treatment of mice with VEGF-DT385 toxin conjugate significantly delayed the onset of tumorigenesis and inhibited solid tumor growth by more than 92%. Furthermore, conjugate treated animals showed less than twice the number of tumor nodules when compared to control mice. Finally, this vascular targeting agent significantly increased survival time of animals by 5 weeks. VEGF-DT385 toxin conjugate resulted in temporary weight loss and no long-lasting toxicity was seen. More importantly, using this established tumor model, VEGF-DT385 toxin conjugate appeared to be as effective as a similar treatment schedule with recombinant human endostatin. Our results suggest that VEGF-DT385 toxin conjugate is a potent inhibitor of mammary adenocarcinoma growth and might be useful in breast cancer therapy.

Original languageEnglish (US)
Pages (from-to)161-171
Number of pages11
JournalBreast Cancer Research and Treatment
Volume85
Issue number2
DOIs
StatePublished - May 1 2004
Externally publishedYes

Fingerprint

Immunotoxins
Vascular Endothelial Growth Factor A
Transgenic Mice
Carcinogenesis
Adenocarcinoma
Breast
Neoplasms
Growth
Endostatins
Human Mammary Glands
Blood Vessels
Weight Loss
Appointments and Schedules
Endothelial Cells
Cell Proliferation
Breast Neoplasms
Survival
Therapeutics

Keywords

  • Angiogenesis
  • Endostatin
  • Mammary carcinoma
  • Tumorigenesis
  • Vascular targeting
  • VEGF-DT385 toxin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

VEGF-DT385 toxin conjugate inhibits mammary adenocarcinoma development in a transgenic mouse model of spontaneous tumorigenesis. / Wild, R.; Yokoyama, Y.; Dings, R. P.M.; Ramakrishnan, Sundaram.

In: Breast Cancer Research and Treatment, Vol. 85, No. 2, 01.05.2004, p. 161-171.

Research output: Contribution to journalArticle

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