A comparison of ocular melanocyte and uveal melanoma cell invasion and the implication of alpha1beta1, alpha4beta1 and alpha6beta1 integrins

Br J Ophthalmol. 2001 Jun;85(6):732-8. doi: 10.1136/bjo.85.6.732.


Background/aims: Posterior uveal melanoma is the most common intraocular tumour in adults, responsible for the death of approximately 35% of patients. Hepatic metastases are most frequent, and once diagnosed survival is usually less than 1 year. The beta1 family of integrins, alphavbeta3 and MMP-2 and MMP-9 have been implicated in the metastasis of several types of tumour. To study their involvement in uveal melanoma we analysed the expression of the beta1 integrins, alphavbeta3, MMP-2, and MMP-9 in 10 primary posterior uveal melanomas, and correlated expression with invasive potential in vitro. Comparable studies were undertaken on cultures of melanocytes.

Methods: Expression of integrins was studied by immunohistochemistry, secretion of MMP-2 and MMP-9 by zymography, and the invasive potential was assessed using a transwell model.

Results: MMP-2 was secreted by all uveal melanomas and seven of 10 secreted MMP-9. Among uveal melanoma, invasion levels of 4-25% were observed and the major integrins expressed were alpha1beta1, alpha2beta1, alpha3beta1, alpha5beta1, and avbeta3. Melanocytes did not express alpha1beta1, alpha4beta1, and alpha6beta1.

Conclusion: The laminin binding alpha6beta1 integrin was not expressed by either melanocytes or tumours with spindle morphology, which are considered to have a better prognosis. It is possible that expression of the alpha6beta1 integrin may prove useful as a prognostic indicator.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cells, Cultured
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Fibronectins / physiology
  • Humans
  • Integrins / metabolism*
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Melanocytes / metabolism*
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Proteins / metabolism*
  • Prognosis
  • Receptors, Vitronectin / metabolism
  • Uveal Neoplasms / metabolism*
  • Uveal Neoplasms / pathology


  • Fibronectins
  • Integrins
  • Neoplasm Proteins
  • Receptors, Vitronectin
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9