血小板源性生长因子受体
番茄红素
成纤维细胞
化学
间质细胞
癌症研究
细胞生物学
血小板衍生生长因子
生长因子
生物
受体
生物化学
体外
抗氧化剂
作者
Han-Sun Chiang,Wen‐Bin Wu,Jia‐You Fang,Der-Fang Chen,Bing‐Huei Chen,Chieh-Chen Huang,Ying-Ting Chen,Chi‐Feng Hung
出处
期刊:Life Sciences
[Elsevier]
日期:2007-11-01
卷期号:81 (21-22): 1509-1517
被引量:36
标识
DOI:10.1016/j.lfs.2007.09.018
摘要
In melanoma development and progression, platelet-derived growth factor (PDGF) has been suggested to modulate the microenvironment, especially stromal fibroblasts, to the benefit of melanoma growth, invasion, and metastasis. Lycopene, a natural carotenoid that is abundant in tomato, has been shown to inhibit proliferation of several types of cancer cells. However, little attention has been paid to skin fibroblasts and melanoma cells. In the present study, we determined the effects of lycopene on stromal fibroblasts and their interactions with melanoma cells. We found that lycopene inhibited PDGF-BB-induced human Hs68 skin fibroblast migration on gelatin and collagen. Further analysis showed that lycopene inhibited PDGF-BB-induced signaling in human Hs68 and primary cultured skin fibroblasts. PDGF-BB-induced phosphorylation of PDGF receptor beta (PDGFR-beta), extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and c-Jun N-terminal kinase (JNK) was attenuated by lycopene in a concentration-dependent manner, whereas the total expression of each protein was not affected. Interestingly, dot binding assay revealed that lycopene could directly bind to human PDGF-BB in PBS and human plasma, indicating that lycopene can bind to PDGF-BB in both in vitro and in vivo conditions. In functional studies, lycopene inhibited melanoma-induced fibroblast migration in a noncontact coculture system and attenuated signaling in fibroblasts simulated by melanoma-derived conditioned medium. Our results provide the first evidence showing that lycopene is an effective inhibitor of migration of stromal fibroblasts and this effect may contribute to its antitumor activity.
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