Serum vascular endothelial growth factor (VEGF) levels correlate with number and location of micrometastases in a murine model of uveal melanoma

Br J Ophthalmol. 2011 Jan;95(1):112-7. doi: 10.1136/bjo.2010.182402. Epub 2010 Sep 6.

Abstract

Background: A preliminary animal study was performed to determine if hepatic micrometastases from uveal melanoma secrete vascular endothelial growth factor (VEGF) that is measurable in serum.

Methods: We analysed the serum of a C57Bl/6 mouse model of uveal melanoma (n=10) at days 4, 7, 14 and 21 post-inoculation for VEGF levels. We compared the serum VEGF levels with the number and location of hepatic micrometastases and their respective expression of VEGF mRNA.

Results: Serum VEGF levels rose after inoculation of C57Bl/6 mice eyes with B16LS9 cutaneous melanoma cells. Beginning on day 14 there was a statistically significant (p<0.05) increase in VEGF levels, rising to an average peak level of 37.985 pg/ml at day 21. Peak serum VEGF levels correlated with the total number of hepatic micrometastases (R=0.444) and there was moderate correlation of peak VEGF serum levels with micrometastases in more hypoxic locations (R=0.572). VEGF mRNA expression by micrometastases was highest in the most hypoxic regions of the hepatic lobule.

Conclusions: Hepatic micrometastastic melanoma arising in a mouse model of ocular melanoma secretes VEGF. The number and location of the micrometastases correlate with serum VEGF levels.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Immunohistochemistry
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / secondary*
  • Melanoma / pathology
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Proteins / metabolism*
  • Uveal Neoplasms / pathology
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Neoplasm Proteins
  • Vascular Endothelial Growth Factor A

Supplementary concepts

  • Uveal melanoma