Coordinate expression of membrane type-matrix metalloproteinases-2 and 3 (MT2-MMP and MT3-MMP) and matrix metalloproteinase-2 (MMP-2) in primary and metastatic melanoma cells

Expression of MMP-2 in melanoma cells has been demonstrated to be involved in the degradation of extracellular matrix during melanoma growth and to correlate with later melanoma metastasis. MMP-2 is considered to be activated by membrane-associated matrix metalloproteinases (MT-MMPs). To know whether MT-MMPs are involved in the activation of MMP-2 in melanoma cells, immunohistochemical studies were performed in primary and metastatic melanoma by use of the antibodies for MT1-MMP, MT2-MMP and MT3-MMP. Expression of MT1-MMP, MT2-MMP, MT3-MMP and MMP-2 in nevocellular nevus (n = 5), dysplastic nevus (n = 2) and juvenile melanoma (n = 3) was undetectable or detected in only a few cells. Superficial spreading melanoma (SSM) (n = 3) and acral lentiginous melanoma (ALM) (n = 3) showed a moderate expression of MT1 similar to3-MMP. In nodular melanoma (NM) (n = 2) and metastatic melanoma (n = 3), MT1 similar to3-MMP was more, intensely expressed. Double immunofluorescence demonstrated a consistent colocalization of MT2-MMP/MMP-2 and MT3-MMP/MMP-2 in the NM and metastatic melanoma cells. The colocalization of MT2,3-MMP and MMP-2 in nodular and metastatic melanoma cells suggests that MT-MMPs and MMP-2 co-operate in the invasive and metastatic process of melanoma cells.