Simple Summary
Adrenomedullin (AM) and AM receptors were immunohistochemically localized in the primitive and metastatic melanoma specimens, suggesting a role of the adrenomedullin system in melanoma growth. Adrenomedullin functions as an autocrine/paracrine growth factor to stimulate proliferation, migration, and invasion of A375, MeWo, and SK-MEL-28 cells, whose effect is inhibited by neutralizing anti-AM and anti-AM receptor antibodies, causing cessation of growth, migration, and invasion in vitro. The in vivo study highlights the significance of adrenomedullin as an important factor that promotes melanoma tumor growth and affects the tumor microenvironment by inducing pathologic neoangiogenesis and lymphangiogenesis. Targeting the adrenomedullin system may provide a rational basis for future therapeutic modalities in melanoma.