1594PCLINICALPATHOLOGICAL CHARACTERISTICS OF CANCER-ASSOCIATED-FIBROBLAST IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA.

Annals of oncology : official journal of the European Society for Medical Oncology(2014)

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ABSTRACT Aim: Cancer associated fibroblasts (CAFs) are a subpopulation of cells that reside within the tumor microenvironment and promotes the transformation process by encouraging tumor growth, neoangiogenesis, modulation of cancer stem cell traits, and formation of metastases. Although CAFs have been observed within the stroma of breast, lung, and pancreas cancers, the precise clinicalpathological characteristics of CAFs in esophageal squamous cell carcinoma (ESCC) remains unclear, and its source is also require further elucidation. Methods: Expression of CAFs markers, a-SMA and S100A4, were examined in 68 ESCC specimens by immunocytochemistry, and the association of a-SMA and S100A4 expression with clinical and pathological features and prognosis were also evaluated. Cell cultured supernate of ESCC cell lines, including Eca-109?TE-1, were collected and then cultured with mesenchymal stem cells (MSCs). Temporal correlation morphological changing of MSCs was observed and expression of a-SMA and S100A4 were also examined by quantitative PCR and Western blot. Results: High a-SMA and S100A4 levels in tumor stroma were expressed in 47.0 % and 42.6 % ESCC samples (32/68 cases, 29/68 cases, respectively), and their expression distribution in each sample was consistent. a-SMA expression correlated significantly with a poorly differentiated phenotype (k2=5.13, P=0.023) and high TNM classification (k2=2.66 P=0.049). Kaplan-Meier plots revealed large differences in OS estimates between patients with high and low a-SMA expression (P=0.029). More importantly, quantitative PCR showed increasing of a-SMA and S100A4 mRNA levels in MSCs after culturing and inducing with cell supernate of Eca-109 and TE-1 cell lines, and Western blot also implied enlargement of a-SMA and S100A4 levels in MSCs after culturing and inducing. Conclusions: There is prominent distribution of CAFs in ESCC tissues, and these CAFs would make a contribution on poor prognosis of patients. Tumor cell induction data demonstrates that mesenchymal stem cells may be the candidate of CAFs in ESCC tissues. The precise mechanisms of CAFs in tumor tissues action in the invasion and metastasis of ESCC require further elucidation. Disclosure: All authors have declared no conflicts of interest.
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