The prognosis of
malignant melanoma is poor due to high incidence of
metastasis, underscoring the demand for development of novel therapeutic strategies. Stress
hormone pro-opiomelanocortin (
POMC) is the precursor for several anti-inflammatory
peptides that hold promise for management of
cancer-related diseases. The present study evaluated the antimetastatic potential and mechanism of
POMC therapy for metastatic
melanoma. Adenovirus-mediated
POMC gene delivery potently inhibited the invasiveness of human and mouse
melanoma cells. Moreover, after induction of lung
metastasis, systemic
POMC expression significantly reduced the foci formation and neovascularization in lungs. Mechanistic studies revealed that
POMC therapy inhibited the epithelial-mesenchymal transition (EMT) of
melanoma cells by upregulation of
E-cadherin and downregulation of
vimentin and α-smooth muscle actin (α-SMA). In addition, microarray analysis unveiled
POMC gene transfer reduced the
mRNA level of multiple prometastatic factors, including
hepatoma-derived growth factor (HDGF). Cell culture and immunohistochemical studies further confirmed that
POMC gene delivery significantly decreased the expression of HDGF in
melanoma cells and tissues. Despite stimulating the invasion and EMT, exogenous HDGF supply only partially attenuated the
POMC-mediated invasion inhibition and EMT change in
melanoma cells. Finally, we delineated the contribution of
melanocortins to
POMC-induced inhibition of invasion, HDGF downregulation, and
E-cadherin upregulation. Together, these results indicate that HDGF downregulation participates in
POMC-induced suppression of
metastasis and EMT in
melanoma.