Soluble Eph A receptors inhibit tumor angiogenesis and progression in vivo

Dana M. Brantley, Nikki Cheng, Erin J. Thompson, Qing Lin, Rolf A. Brekken, Philip E. Thorpe, Rebecca S. Muraoka, Douglas Pat Cerretti, Ambra Pozzi, Dowdy Jackson, Charles Lin, Jin Chen

Research output: Contribution to journalArticle

268 Citations (Scopus)

Abstract

The Eph family of receptor tyrosine kinases and their ligands, known as ephrins, play a crucial role in vascular development during embryogenesis. The function of these molecules in adult angiogenesis has not been well characterized. Here, we report that blocking Eph A class receptor activation inhibits angiogenesis in two independent tumor types, the RIP-Tag transgenic model of angiogenesis-dependent pancreatic islet cell carcinoma and the 4T1 model of metastatic mammary adenocarcinoma. Ephrin-A1 ligand was expressed in both tumor and endothelial cells, and EphA2 receptor was localized primarily in tumor-associated vascular endothelial cells. Soluble EphA2-Fc or EphA3-Fc receptors inhibited tumor angiogenesis in cutaneous window assays, and tumor growth in vivo. EphA2-Fc or EphA3-Fc treatment resulted in decreased tumor vascular density, tumor volume, and cell proliferation, but increased cell apoptosis. However, EphA2-Fc had no direct effect on tumor cell growth or apoptosis in culture, yet inhibited migration of endothelial cells in response to tumor cells, suggesting that the soluble receptor inhibited blood vessel recruitment by the tumor. These data provide the first functional evidence for Eph A class receptor regulation of pathogenic angiogenesis induced by tumors and support the function of A class Eph receptors in tumor progression.

Original languageEnglish (US)
Pages (from-to)7011-7026
Number of pages16
JournalOncogene
Volume21
Issue number46
DOIs
StatePublished - Oct 10 2002

Fingerprint

Eph Family Receptors
Neoplasms
Endothelial Cells
EphA3 Receptor
Blood Vessels
Ephrin-A1
EphA2 Receptor
Islet Cell Carcinoma
Ephrins
Vascular Tissue Neoplasms
Apoptosis
Ligands
Fc Receptors
Growth
Tumor Burden
Islets of Langerhans
Embryonic Development
Adenocarcinoma
Breast
Cell Proliferation

Keywords

  • Eph receptor tyrosine kinase
  • Ephrin
  • Soluble Eph receptor
  • Tumor angiogenesis
  • Vascular window model

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Brantley, D. M., Cheng, N., Thompson, E. J., Lin, Q., Brekken, R. A., Thorpe, P. E., ... Chen, J. (2002). Soluble Eph A receptors inhibit tumor angiogenesis and progression in vivo. Oncogene, 21(46), 7011-7026. https://doi.org/10.1038/sj.onc.1205679

Soluble Eph A receptors inhibit tumor angiogenesis and progression in vivo. / Brantley, Dana M.; Cheng, Nikki; Thompson, Erin J.; Lin, Qing; Brekken, Rolf A.; Thorpe, Philip E.; Muraoka, Rebecca S.; Cerretti, Douglas Pat; Pozzi, Ambra; Jackson, Dowdy; Lin, Charles; Chen, Jin.

In: Oncogene, Vol. 21, No. 46, 10.10.2002, p. 7011-7026.

Research output: Contribution to journalArticle

Brantley, DM, Cheng, N, Thompson, EJ, Lin, Q, Brekken, RA, Thorpe, PE, Muraoka, RS, Cerretti, DP, Pozzi, A, Jackson, D, Lin, C & Chen, J 2002, 'Soluble Eph A receptors inhibit tumor angiogenesis and progression in vivo', Oncogene, vol. 21, no. 46, pp. 7011-7026. https://doi.org/10.1038/sj.onc.1205679
Brantley DM, Cheng N, Thompson EJ, Lin Q, Brekken RA, Thorpe PE et al. Soluble Eph A receptors inhibit tumor angiogenesis and progression in vivo. Oncogene. 2002 Oct 10;21(46):7011-7026. https://doi.org/10.1038/sj.onc.1205679
Brantley, Dana M. ; Cheng, Nikki ; Thompson, Erin J. ; Lin, Qing ; Brekken, Rolf A. ; Thorpe, Philip E. ; Muraoka, Rebecca S. ; Cerretti, Douglas Pat ; Pozzi, Ambra ; Jackson, Dowdy ; Lin, Charles ; Chen, Jin. / Soluble Eph A receptors inhibit tumor angiogenesis and progression in vivo. In: Oncogene. 2002 ; Vol. 21, No. 46. pp. 7011-7026.
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