Inhibition of Ocular Tumor and Endothelial Cell Growth with a TEAD4216 Peptide Fragment

Authors

  • Bissan Ahmed Arab International University
  • Andrew Stempel Casey Eye Institute, OHSU, Portland
  • Trevor J. McFarland Schepens Eye Research Institute, Harvard Medical School, Boston
  • Bruce Ksander Schepens Eye Research Institute, Harvard Medical School, Boston
  • Binoy Appukuttan Flinders University, SA,
  • Tim Stout Cullen Eye Institute, Baylor College of Medicine Houston, TX,

Abstract

Purpose: Transcriptional enhancer factor 1-related (RTEF-1) also known as TEAD4 is expressed in ocular vascular endothelial cells and plays a role in the control of VEGF expression. Alternative processing of TEAD4 hnRNA results in different proteins able to stimulate or inhibit VEGF gene transcription. The purpose of this study is to test whether short peptide fragments (STY-RMR), representing functional domains of the inhibitory TEAD4216 isoform, can inhibit tumor as well as endothelial cell proliferation.

Experimental Design: Cell proliferation was assessed using a colorimetric assay in cell lines incubated with STY-RMR, the amount of secreted VEGF within media was determined both in treated and control cell lines.

Results: Significant dose dependent inhibition of cell proliferation was observed. Maximal inhibition of ocular melanoma (Mel 202 and Mel 207) cell proliferation was observed at a dose of 30 mg/100ml of STY-RMR (87% and 60% inhibition, respectively). At the same dose, more than 50% inhibition was observed in retinoblastoma and breast cancer cells (P <0.001). Significant inhibition of primate ocular endothelial cell proliferation (42% at 30 mg/100 ml (p < 0.001), and retinal pigment epithelial cells showed also a 75% inhibition (p = 0.007). Secreted VEGF was decreased in the media of all tested cell lines that had been exposed to STY-RMR.

Conclusion: Functional short peptide domains derived from the TEAD4216 isoform may prove to be useful for treatment of ocular tumors and other VEGF dependent neovascular disease.

Inhibition of proliferation and VEGF production within ocular endothelial cells indicate the potential of this agent to treat age-related macular degeneration (ARMD) and diabetic retinopathy (DR).

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Published

2018-10-31

Issue

Vol. 5 (2018)

Section

Articles

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