Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant digestive tumor with a very poor prognosis. Hypoxia-inducible transcription factor-1α (HIF-1α) is involved in malignant progression in many solid tumors, including PDAC, upregulation of HIF-1α accelerates PDAC progression, but the exact regulatory mechanisms of HIF-1αin PDAC has not been unequivocally addressed. Recently, an increasing number of studies reported that toll-like receptors (TLRs) were upregulated in epithelial malignancies and involved in tumor progression, but whether TLRs, such as TLR4, is expressed on PDAC cells remains unknown. In immune-related cells, TLR signal pathway may induce expression of HIF-1α, but it is also still unclear whether there exists some association between TLR4 and HIF-1α in tumor microenviroment, such as PDAC.
A research article to be published on June 21, 2010 in the World Journal of Gastroenterology addresses this question. The research team led by He-Shui Wu, MD, from Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, used real time polymerase chain reaction and immunohistochemistry, to detect TLR4, NF-κB p65 and HIF-1α expression in 65 cases of PDAC tissues and 38 cases of corresponding adjacent tissues.
Their study revealed that TLR4, NF-κB p65 and HIF-1α were overexpressed in PDAC. The expression of TLR4 and HIF-1α was associated with tumor size, lymph node metastasis, venous invasion and pathological stage. Furthermore, the expression of TLR4 was positively correlated with expression of HIF-1α. Thus, TLR4 may be a novel marker for the progression and prognosis of PDAC, and may provide a new strategy for therapeutic intervention in the treatment of patients with PDAC in the future.
Based on these results and previous reports, the authors speculated that active TLR4 signal pathway may be partly involved in up-regulating HIF-1α in PDAC tumor microenviroment via NF-κB pathway, and promoted progression of PDAC. These results demonstrated a new view of molecules involved in regulatory mechanism of HIF-1α and thus may provide new therapeutic targets for PDAC.
Reference: Zhang JJ, Wu HS, Wang L, Tian Y, Zhang JH, Wu HL. Expression and significance of TLR4 and HIF-1α in pancreatic ductal adenocarcinoma. World J Gastroenterol 2010; 16(23): 2881-2888
Correspondence to: He-Shui Wu, MD, Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China. firstname.lastname@example.org
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World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H pylori infection and provides a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2009 IF: 2.092. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.
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