Systemic pro-opiomelanocortin expression induces melanogenic differentiation and inhibits tumor angiogenesis in established mouse melanoma.
Malignant melanoma is one of the leading causes of cancer mortality worldwide, underlining the need for effective novel therapies. In this study, the therapeutic efficacy and mechanism of systemic pro-opiomelanocortin (POMC) therapy were evaluated in mice bearing established melanoma. Injection of adenovirus encoding POMC (Ad-POMC) led to hepatic POMC overexpression and elevated adrenocorticotropin (ACTH) levels in the circulation. Systemic POMC therapy significantly attenuated the growth of established melanoma and prolonged the survival of tumor-bearing mice. Histological analysis revealed that systemic POMC therapy induced melanogenic differentiation while reducing melanoma growth. In addition, POMC therapy also elicited a significant reduction in the neovascular network of melanoma. Last, we demonstrated that POMC-derived peptides, including ACTH, α-melanocyte-stimulating hormone (α-MSH), and β-MSH, are involved in POMC-mediated melanogenic differentiation and angiogenesis inhibition. In summary, systemic POMC therapy suppresses melanoma growth via induction of melanogenic differentiation and angiogenesis blockade, thereby demonstrating its potential as a novel treatment modality for melanoma.
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan.
Guei-Sheung
GS
Liu
Han-En
HE
Tsai
Wen-Tsan
WT
Weng
Li-Feng
LF
Liu
Chien-Hui
CH
Weng
Ming-Ru
MR
Chuang
Hing-Chung
HC
Lam
Chieh-Shan
CS
Wu
Richard
R
Tee
Zhi-Hong
ZH
Wen
Shen-Long
SL
Howng
Ming-Hong
MH
Tai
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D018450:Disease Progression; D042783:Endothelial Cells / Q000166:cytology; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D008546:Melanoma, Experimental / Q000098:blood supply / Q000473:pathology / Q000628:therapy* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000503:physiopathology; D011333:Pro-Opiomelanocortin / Q000235:genetics* / Q000378:metabolism*; D016019:Survival Analysis; D023041:Xenograft Model Antitumor Assays
D011333:Pro-Opiomelanocortin