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Given that PDE5A down-regulation increased invasiveness and that PDE5A expression was higher in primary tumors than in metastatic tumors, it is biologically plausible that PDE5A inhibitors may promote invasion of primary tumors. The previous study tested melanoma cell lines mostly of metastatic origin and did not test invasive potential of cells from primary tumors.8 However, because primary tumors expressed substantially higher levels of PDE5A than did metastatic melanomas, the effect may be more marked. Melanoma is highly heterogeneous in its characteristics, unlike cell lines,36 so even a small population of cells that respond strongly could be significant. Our study included only confirmed invasive melanomas in the radial and/or vertical growth phase, and our findings suggest an association of PDE5A inhibitors with the risk of melanoma development. The association of PDE5A inhibitors with melanoma progression, recurrence, and metastasis might be stronger, warranting further studies. cialis 40mg leukaemia (cancer of the blood cells)

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