A comparison of ocular melanocyte and uveal melanoma cell invasion and the implication of α1β1, α4β1 and α6β1 integrins

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, alphav beta3 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, alphav beta3, 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 alpha1 beta1, alpha2 beta1, alpha3 beta1, alpha5 beta1, and av beta3. Melanocytes did not express alpha1 beta1, alpha4 beta1, and alpha6 beta1. Conclusion-The laminin binding alpha6 beta1 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 alpha6 beta1 integrin may prove useful as a prognostic indicator.