The vascular-ablative agent VEGF121/rGel inhibits pulmonary metastases of MDA-MB-231 breast tumors

Sophia Ran, Khalid A. Mohamedali, Troy A. Luster, Philip E. Thorpe, Michael G. Rosenblum

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

VEGF121/rGel, a fusion protein composed of the growth factor VEGF121 and the recombinant toxin gelonin (rGel), targets the tumor neovasculature and exerts impressive cytotoxic effects by inhibiting protein synthesis. We evaluated the effect of VEGF121/rGel on the growth of metastatic MDA-MB-231 tumor cells in SCID mice. VEGF121/rGel treatment reduced surface lung tumor foci by 58% compared to controls (means were 22.4 and 53.3, respectively; P < .05) and the mean area of lung colonies by 50% (210 ± 37 m2 vs 415 ± 10 m2 for VEGF121/rGel and control, respectively; P < .01). In addition, the vascularity of metastatic foci was significantly reduced (198 ± 37 vs 388 ± 21 vessels/mm2 for treated and control, respectively). Approximately 62% of metastatic colonies from the VEGF121/rGel- treated group had fewer than 10 vessels per colony compared to 23% in the control group. The VEGF receptor Flk-1 was intensely detected on the metastatic vessels in the control but not in the VEGF121/rGel-treated group. Metastatic foci present in lungs had a three-fold lower Ki-67 labeling index compared to control tumors. Thus, the antitumor vascular-ablative effect of VEGF121/rGel may be utilized not only for treating primary tumors but also for inhibiting metastatic spread and vascularization of metastases.

Original languageEnglish (US)
Pages (from-to)486-496
Number of pages11
JournalNeoplasia
Volume7
Issue number5
DOIs
StatePublished - May 2005

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Blood Vessels
Breast Neoplasms
Neoplasm Metastasis
Lung
Neoplasms
Vascular Endothelial Growth Factor Receptor-2
SCID Mice
Gelonium multiflorum GEL protein
Intercellular Signaling Peptides and Proteins
Proteins
Control Groups
Growth

Keywords

  • Fusion toxin
  • Gelonin
  • Metastatic breast tumors
  • Vascular targeting
  • VEGF

ASJC Scopus subject areas

  • Cancer Research

Cite this

Ran, S., Mohamedali, K. A., Luster, T. A., Thorpe, P. E., & Rosenblum, M. G. (2005). The vascular-ablative agent VEGF121/rGel inhibits pulmonary metastases of MDA-MB-231 breast tumors. Neoplasia, 7(5), 486-496. https://doi.org/10.1593/neo.04631

The vascular-ablative agent VEGF121/rGel inhibits pulmonary metastases of MDA-MB-231 breast tumors. / Ran, Sophia; Mohamedali, Khalid A.; Luster, Troy A.; Thorpe, Philip E.; Rosenblum, Michael G.

In: Neoplasia, Vol. 7, No. 5, 05.2005, p. 486-496.

Research output: Contribution to journalArticle

Ran, S, Mohamedali, KA, Luster, TA, Thorpe, PE & Rosenblum, MG 2005, 'The vascular-ablative agent VEGF121/rGel inhibits pulmonary metastases of MDA-MB-231 breast tumors', Neoplasia, vol. 7, no. 5, pp. 486-496. https://doi.org/10.1593/neo.04631
Ran, Sophia ; Mohamedali, Khalid A. ; Luster, Troy A. ; Thorpe, Philip E. ; Rosenblum, Michael G. / The vascular-ablative agent VEGF121/rGel inhibits pulmonary metastases of MDA-MB-231 breast tumors. In: Neoplasia. 2005 ; Vol. 7, No. 5. pp. 486-496.
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