title: Up-regulation of hepatoma-derived growth factor facilitates tumor progression in malignant melanoma [corrected].
abstract: Cutaneous malignant melanoma is the fastest increasing malignancy in humans. Hepatoma-derived growth factor (HDGF) is a novel growth factor identified from human hepatoma cell line. HDGF overexpression is correlated with poor prognosis in various types of cancer including melanoma. However, the underlying mechanism of HDGF overexpression in developing melanoma remains unclear. In this study, human melanoma cell lines (A375, A2058, MEL-RM and MM200) showed higher levels of HDGF gene expression, whereas human epidermal melanocytes (HEMn) expressed less. Exogenous application of HDGF stimulated colony formation and invasion of human melanoma cells. Moreover, HDGF overexpression stimulated the degree of invasion and colony formation of B16-F10 melanoma cells whereas HDGF knockdown exerted opposite effects in vitro. To evaluate the effects of HDGF on tumour growth and metastasis in vivo, syngeneic mouse melanoma and metastatic melanoma models were performed by manipulating the gene expression of HDGF in melanoma cells. It was found that mice injected with HDGF-overexpressing melanoma cells had greater tumour growth and higher metastatic capability. In contrast, mice implanted with HDGF-depleted melanoma cells exhibited reduced tumor burden and lung metastasis. Histological analysis of excised tumors revealed higher degree of cell proliferation and neovascularization in HDGF-overexpressing melanoma. The present study provides evidence that HDGF promotes tumor progression of melanoma and targeting HDGF may constitute a novel strategy for the treatment of melanoma.
authors.affiliation: Institute of Biomedical Science, National Sun Yat-sen University, Kaohsiung, Taiwan.
authors.forename: Han-En
authors.initials: HE
authors.lastname: Tsai
authors.forename: Jian-Ching
authors.initials: JC
authors.lastname: Wu
authors.forename: Mei-Lang
authors.initials: ML
authors.lastname: Kung
authors.forename: Li-Feng
authors.initials: LF
authors.lastname: Liu
authors.forename: Lai-Hsin
authors.initials: LH
authors.lastname: Kuo
authors.forename: Hsiao-Mei
authors.initials: HM
authors.lastname: Kuo
authors.forename: San-Cher
authors.initials: SC
authors.lastname: Chen
authors.forename: Elsa C
authors.initials: EC
authors.lastname: Chan
authors.forename: Chieh-Shan
authors.initials: CS
authors.lastname: Wu
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Tai
authors.forename: Guei-Sheung
authors.initials: GS
authors.lastname: Liu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C051610:hepatoma-derived growth factor
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