Immunolocalisation studies of matrix metalloproteinases-1,-2 and-3 in human melanoma

The matrix metalloproteinases (MMPs) are considered to have an important ro le in connective tissue degradation and have been implicated in the mechani sms of tumour invasion and metastatic spread. We have used immunohistochemi stry to examine and compare the tissue distributions of collagenase-1 (MMP- 1), gelatinase A (MMP-2) and stromelysin-1 (MMP-3) in 18 specimens of malig nant melanoma, viz. 10 superficial spreading and 8 nodular melanomas. MMPs- 1, -2 and -3 were demonstrated within melanoma and host tissue cells, espec ially at the periphery of some rumours, but were usually restricted to less than 10% of total melanoma cells. The MMPs were absent from 'normal' skin tissue distant from the tumour. MMP-2 was localised to discrete groups of c ells and was especially evident at the epidermal:tumour interface, whereas MMP-3 was mainly confined to the deeper margins of melanoma. No regular pat tern of MMP expression was observed for either the superficial spreading or the nodular melanomas. The variable distributions of the MMPs suggested th at enzyme expression was subject to local microenvironmental regulation, po ssibly in response to matrix components and the cellular heterogeneity obse rved at the tumour margins. These in situ observations add weight to the co ncept that specific MMPs contribute to the mechanisms of tumour invasion.