A comparison of ocular melanocyte and uveal melanoma cell invasion and the implication of α1β1, α4β1 and α6β1 integrins
- Shona R Elshawa,
- Karen Sisleya,
- Neil Crossb,
- Anna K Murrayb,
- Shiela M MacNeilc,
- Mark Wagnerc,
- Carmel E Nicholsa,
- Ian G Renniea
- aDepartment of Ophthalmology and Orthoptics, University of Sheffield, Hallamshire Hospital, Sheffield S10 2JF, UK, bInstitute for Cancer Studies, University of Sheffield, Medical School, Sheffield S10 2RX, UK, cDivision of Clinical Sciences, Section of Medicine, Northern General Hospital, Sheffield, S5 , UK
- K Sisley, University of Sheffield, Department of Ophthalmology and Orthoptics, O Floor, Royal Hallamshire Hospital, Sheffield S10 2JF, UK
- Accepted 3 January 2001
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 β1 family of integrins, αvβ3 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 β1 integrins, αvβ3, 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 α1β1, α2β1, α3β1, α5β1, and avβ3. Melanocytes did not express α1β1, α4β1, and α6β1.
CONCLUSION The laminin binding α6β1 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 α6β1 integrin may prove useful as a prognostic indicator.