RRC ID |
45429
|
著者 |
Kasamatsu A, Uzawa K, Minakawa Y, Ishige S, Kasama H, Endo-Sakamoto Y, Ogawara K, Shiiba M, Takiguchi Y, Tanzawa H.
|
タイトル |
Decorin in human oral cancer: a promising predictive biomarker of S-1 neoadjuvant chemosensitivity.
|
ジャーナル |
Biochem Biophys Res Commun
|
Abstract |
We reported previously that decorin (DCN) is significantly up-regulated in chemoresistant cancer cell lines. DCN is a small leucine-rich proteoglycan that exists and functions in stromal and epithelial cells. Accumulating evidence suggests that DCN affects the biology of several types of cancer by directly/indirectly targeting the signaling molecules involved in cell growth, survival, metastasis, and angiogenesis, however, the molecular mechanisms of DCN in chemoresistance and its clinical relevance are still unknown. Here we assumed that DCN silencing cells increase chemosusceptibility to S-1, consisted of tegafur, prodrug of 5-fluorouracil. We first established DCN knockdown transfectants derived from oral cancer cells for following experiments including chemosusceptibility assay to S-1. In addition to the in vitro data, DCN knockdown zenografting tumors in nude mice demonstrate decreasing cell proliferation and increasing apoptosis with dephosphorylation of AKT after S-1 chemotherapy. We also investigated whether DCN expression predicts the clinical responses of neoadjuvant chemotherapy (NAC) using S-1 (S-1 NAC) for oral cancer patients. Immunohistochemistry data in the preoperative biopsy samples was analyzed to determine the cut-off point for status of DCN expression by receiver operating curve analysis. Interestingly, low DCN expression was observed in five (83%) of six cases with complete responses to S-1 NAC, and in one (10%) case of 10 cases with stable/progressive disease, indicating that S-1 chemosensitivity is dramatically effective in oral cancer patients with low DCN expression compared with high DCN expression. Our findings suggest that DCN is a key regulator for chemoresistant mechanisms, and is a predictive immunomarker of the response to S-1 NAC and patient prognosis.
|
巻・号 |
457(1)
|
ページ |
71-6
|
公開日 |
2015-1-30
|
DOI |
10.1016/j.bbrc.2014.12.093
|
PII |
S0006-291X(14)02282-7
|
PMID |
25550184
|
MeSH |
Aged
Aged, 80 and over
Animals
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use
Biomarkers, Tumor / metabolism*
Biopsy
Cell Line, Tumor
Decorin / metabolism*
Drug Combinations
Female
Gene Knockdown Techniques
Humans
Immunoblotting
Immunohistochemistry
Male
Mice, Nude
Middle Aged
Mouth Neoplasms / drug therapy*
Mouth Neoplasms / metabolism*
Mouth Neoplasms / pathology
Neoadjuvant Therapy*
Neoplasms, Squamous Cell / drug therapy
Neoplasms, Squamous Cell / metabolism
Neoplasms, Squamous Cell / pathology
Oxonic Acid / pharmacology
Oxonic Acid / therapeutic use*
Tegafur / pharmacology
Tegafur / therapeutic use*
Xenograft Model Antitumor Assays
|
IF |
2.985
|
引用数 |
10
|
WOS 分野
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
リソース情報 |
ヒト・動物細胞 |
Sa3(RCB0980) |