Premium
Insulin‐like growth factor binding protein‐5 (IGFBP‐5) suppresses the tumourigenesis of head and neck squamous cell carcinoma
Author(s) -
Hung PS,
Kao SY,
Shih YH,
Chiou SH,
Liu CJ,
Chang KW,
Lin SC
Publication year - 2008
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2280
Subject(s) - head and neck squamous cell carcinoma , cancer research , gene knockdown , insulin like growth factor binding protein , growth factor , cell growth , insulin like growth factor , biology , cancer , metastasis , medicine , cell culture , head and neck cancer , receptor , genetics
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. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.