Insulin-like growth factor binding protein-5 (IGFBP-5) suppresses the tumourigenesis of head and neck squamous cell carcinoma.
Head and neck squamous cell carcinoma (HNSCC) is a global malignancy. The insulin-like growth factor (IGF) signalling axis plays a critical role in tumourigenesis. This study defined the clinical and functional roles of insulin-like growth factor binding protein-5 (IGFBP-5) in HNSCC. Down-regulation of IGFBP-5 mRNA expression was found during the progression from pre-cancer to HNSCC. The down-regulation in HNSCC was associated with a higher propensity to nodal metastasis. SAS and OECM-1 are HNSCC cells that do, or do not, express IGFBP-5, respectively. Recombinant IGFBP-5 reduced the proliferation of OECM-1 cells and this was exerted mainly through blockade of the IGF pathways. Either IGFBP-5 or IGF-I treatment alone promoted OECM-1 migration, but a combination of treatments generated antagonistic effects. Overexpression of IGFBP-5 reduced the proliferation and anchorage-independent growth of both OECM-1 and SAS cells. Conversely, knockdown of IGFBP-5 expression significantly induced the proliferation and anchorage-independent growth of SAS cells. It also induced the growth of xenografted SAS tumours. SAS transfectants that expressed mutant or truncated IGFBP-5, which lack IGF binding activity, exhibited significantly lower anchorage-independent growth than vector control. This suggests that IGFBP-5 possesses an IGF-independent suppressor function. The suppressive effects of IGFBP-5 on the tumourigenesis of HNSCC might be invaluable to future neoplastic intervention.
Hung
P-S
PS
Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Taipei, Taiwan.
Kao
S-Y
SY
Shih
Y-H
YH
Chiou
S-H
SH
Liu
C-J
CJ
Chang
K-W
KW
Lin
S-C
SC
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000235:genetics / Q000502:physiology* / Q000627:therapeutic use; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D034622:RNA Interference; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014161:Transduction, Genetic
D018975:Insulin-Like Growth Factor Binding Protein 5; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II