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)