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World J Gastroenterol. May 7, 2010; 16(17): 2080-2093
Published online May 7, 2010. doi: 10.3748/wjg.v16.i17.2080
Connection between inflammation and carcinogenesis in gastrointestinal tract: Focus on TGF-β signaling
Suntaek Hong, Ho-Jae Lee, Seong Jin Kim, Ki-Baik Hahm
Suntaek Hong, Laboratory of Cancer Cell Biology, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon 406-840, South Korea
Ho-Jae Lee, Laboratory of Chemoprevention, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon 406-840, South Korea
Seong Jin Kim, Laboratory of Cell Regulation and Carcinogenesis, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon 406-840, South Korea
Ki-Baik Hahm, Laboratory of Translational Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon 406-840, South Korea; Department of Gastroenterology, Gachon Graduate School of Medicine, Incheon 406-840, South Korea
Author contributions: Hong S wrote the manuscript; Lee HJ contributed to article processing; Kim SJ mentored all the research regarding TGF-β; Hahm KB organized, revised and orchestrated the manuscript.
Supported by The Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST), No. 20090081756
Correspondence to: Ki-Baik Hahm, MD, PhD, Laboratory of Translational Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon 406-840, South Korea. hahmkb@gachon.ac.kr
Telephone: +82-32-8996055 Fax: +82-32-8996054
Received: December 30, 2009
Revised: February 4, 2010
Accepted: February 11, 2010
Published online: May 7, 2010
Abstract

Inflammation is a primary defense process against various extracellular stimuli, such as viruses, pathogens, foods, and environmental pollutants. When cells respond to stimuli for short periods of time, it results in acute or physiological inflammation. However, if the stimulation is sustained for longer time or a pathological state occurs, it is known as chronic or pathological inflammation. Several studies have shown that tumorigenesis in the gastrointestinal (GI) tract is closely associated with chronic inflammation, for which abnormal cellular alterations that accompany chronic inflammation such as oxidative stresses, gene mutations, epigenetic changes, and inflammatory cytokines, are shared with carcinogenic processes, which forms a critical cross-link between chronic inflammation and carcinogenesis. Transforming growth factor (TGF)-β is a multi-potent cytokine that plays an important role in regulation of cell growth, apoptosis and differentiation. Most importantly, TGF-β is a strong anti-inflammatory cytokine that regulates the development of effector cells. TGF-β has a suppressive effect on carcinogenesis under normal conditions by inhibiting abnormal cell growth, but on the other hand, many GI cancers originate from uncontrolled cell growth and differentiation by genetic loss of TGF-β signaling molecules or perturbation of TGF-β adaptors. Once a tumor has developed, TGF-β exerts a promoting effect on the tumor itself and stromal cells to enhance cell growth, alter the responsiveness of tumor cells to stimulate invasion and metastasis, and inhibited immune surveillance. Therefore, novel development of therapeutic agents to inhibit TGF-β-induced progression of tumor and to retain its growth inhibitory activities, in addition to anti-inflammatory actions, could be useful in oncology. In this review, we discuss the role of TGF-β in inflammation and carcinogenesis of the GI tract related to abnormal TGF-β signaling.

Keywords: Inflammation; Carcinogenesis; Transforming growth factor-β; Gastrointestinal tract