Since we found an increased MMP3 secretion in the NHE1 overexpressing cells and because in a wide variety of cancers including melanoma cells NHE1 activity is considerably elevated [1, 3, 57, 58], it is conceivable that the number of H+ ions released at the cell surface may be high enough to sufficiently stimulate the sphingomyelin-converting enzymes (and through SPC indirectly MMP3) even though neither the proper nor a large-area pH optimum is reached. This evidence concerns the gene MMP3 and melanoma.