ABSTRACT
【Objective】 To investigate the effects of gallbladder cancer-associated fibroblasts (CAFs) on the migration of lymphatic endothelial cells (LECs) so as to elucidate the molecular mechanisms involved. 【Methods】 The CAFs and normal fibroblasts (NFs) were extracted by enzymatic digestion, and the supernatant (CM) of CAFs and NFs was collected. The levels of IL-6, IGFBP3 and other related cytokines were detected by semi-quantitative protein factor microarray and ELISA. The expressions of α-SMA (CAFs maker) and IGFBP3 in gallbladder cancer and para-cancer tissues were detected by immunohistochemistry, and the correlation of α-SMA and IGFBP3 expressions with clinicopathological characteristics were analyzed. LECs were cultured and divided into serum-free medium group (control group), CAF-CM co-culture group, NF-CM co-culture group, IGFBP3 group, and CAF-CM+IGFBP3 inhibitor (2-Deoxy-D-glucose, 2-DG) group according to different treatment. Transwell migration assays and wound healing assays were applied to analyze the migration ability of LECs under different treatment. The expressions of E-cadherin, N-cadherin and Vimentin were detected by Western blotting. 【Results】 Protein factor microarray and ELISA showed that the concentration of IGFBP3 in CAF-CM was significantly increased, and the expression of α-SMA was significantly related to lymph node metastasis, advanced TNM stage and expression of IGFBP3. IGFBP3 secreted from CAF-CM significantly promoted LECs migration, up-regulated the expression of N-cadherin and Vimentin, and down-regulated the expression of E-cadherin. Treatment with IGFBP3 inhibitor 2-DG could reverse the effect of CAF-CM on migration of LECs and related protein expressions. 【Conclusion】 Gallbladder CAFs promote the migration of LECs via releasing IGFBP3, which affects EMT transformation.
ABSTRACT
Gallbladder cancer (GBC) is the most common malignancy of the biliary tract.Most patients are diagnosed at the advanced stage,missing the optimal chance for curative surgery,thus leading to the fact that GBC is usually associated with poor prognosis.It is very crucial to strengthen the basic research on GBC,which may further improve the diagnosis and treatment.The research updates on the related genes in the initiation and progression,molecular mechanism of lymphatic metastasis,and tumor microenvironment of GBC in recent years were reviewed in this paper.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of cancer-associated fibroblasts (CAFs) on the growth and invasion of gallbladder cancer cells.</p><p><b>METHODS</b>The CAFs were isolated from human primary gallbladder carcinoma tissues by tissue culture and digestion methods. The cells were purified by differential adhesion method, and the primary cells were identified morphologically and immunocytochemically. The proliferation and invasion of two human gallbladder carcinoma cell lines (SBC-996 and GBC-SD) co-cultured with CAFs were detected by MTT and Transwell chamber assays.</p><p><b>RESULTS</b>Gallbladder carcinoma CAFs were isolated successfully by both tissue culture and enzyme digestion methods, and the latter method was more convenient and efficient. MTT and Transwell assays showed that CAFs significantly promoted the proliferation and invasion of the two gallbladder carcinoma cell lines.</p><p><b>CONCLUSION</b>CAFs can promote the proliferation and invasion of gallbladder carcinoma cells in vitro, suggesting the important role of CAFs in the development of gallbladder carcinoma.</p>
Subject(s)
Humans , Carcinoma , Pathology , Cell Line, Tumor , Cell Proliferation , Coculture Techniques , Fibroblasts , Cell Biology , Gallbladder Neoplasms , PathologyABSTRACT
<p><b>OBJECTIVE</b>To analyze the clinical features of patients with gallbladder cancer from 17 hospitals in 5 Northwestern provinces (autonomous region) of China from 2009 to 2013.</p><p><b>METHODS</b>A total of 2 379 cases with gallbladder cancer in 17 tertiary hospitals from 5 Northwestern provinces of China from January 2009 to December 2013 were reviewed retrospectively. The clinical data was collected by standardized "Questionnaire for Clinical Survey of Gallbladder Cancer in Northwestern Area of China". χ² test was used to analyze the data.</p><p><b>RESULTS</b>(1) Gallbladder cancer from 17 hospitals accounted for 1.6%-6.8% of all bile tract diseases from 2009 to 2013 in Northwestern China, average was 2.7%. Gallbladder cancer accounted for 0.4%-0.9% of abdominal surgery, average was 0.7%. (2) The incidence of gallbladder cancer was higher in the aged females, the ration of female to male was 1.0 to 2.1. The average age of gallbladder cancer was (64 ± 11) years. The occupation of patients was mainly farmers (χ² = 147.10, P < 0.01). (3) 57.2% of the gallbladder cancers were associated with gallstones. (4) The main pathological patterns of gallbladder cancer were moderate and poor differentiated adenocarcinoma, showing an aggressive malignancy. TNM stage IV accounted for 55.1% of all cases, which was associated with the poor prognosis. (5) The curative resection rate was 30.4%.</p><p><b>CONCLUSIONS</b>Gallbladder cancer is common in the aged females and mainly at advanced stage. The screening and follow-up of high-risk groups with ultrasound and other methods regularly could increase the early diagnosis rate of gallbladder cancer, aggressive surgical resection combined with other comprehensive treatment could improve the prognosis of patients.</p>