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

Thyrotrophin and thyroid-stimulating immunoglobulins have similar characteristics in activating human thyroid membrane adenylate cyclase.

The activation of adenylate cyclase by TSH and thyroid-stimulating immunoglobulins (TSIg) was investigated in membranes prepared from non-toxic goitres. The assay conditions for maximal adenylate cyclase stimulation by TSH in the absence and presence of a cell cytosol preparation were determined. Cell cytosol had no detectable effect on the characteristics of activation by TSH although it increased the production of cyclic AMP in response to the hormone. In the presence of cell cytosol, membrane protein, pH and substrate concentration dependency of adenylate cyclase activation by both TSH and TSIg were similar. In a comparison of the time-courses of activation there was no apparent lag phase in the activation of adenylate cyclase by TSIg but the onset of activation was slower and linearity persisted longer than with TSH.