| 抄録 |
Epidemiological and experimental data highlight a connection between inflammation and tumorigenesis. Tumors are infiltrated by immune cells and the process of tumor-associated inflammation impacts most, if not all, stages of tumorigenesis, both in inflammation-associated cancers and in cancers which initially arise in the absence of underlying inflammation. In the past 7-10 years, we have explored the identity of some of the molecular entities that serve as critical links between inflammatory cells and cancer cells. Using mouse models of colitis-associated cancer (CAC) and spontaneous colorectal cancer (CRC), we have demonstrated that inflammatory cytokines control tumor initiation, promotion and progression. Cytokines such as Interleukin-6 (IL-6) have profound effects on cancer cells by activating transcription factor STAT3, which controls a genetic program that stimulates cell survival and proliferation. Other cytokines, such as IL-23, do not signal directly to epithelial cells but are critical for shaping the tumor environment and for stimulating the production of downstream pro-tumorigenic effector cytokines, such as IL-6, IL-17 and IL-22. Another cancer studied in our laboratory is hepatocellular carcinoma (HCC). Again, we have demonstrated a critical role for IL-6 in the development of chemically-induced HCC and these studies have led to the current recognition that IL-6 also plays a master role in human hepatocellular carcinogenesis. Mechanistically, most of tumor-promoting properties of cytokines lie in their ability to trigger activation of either STAT3 or NF-κB, which also controls cell survival. The role of IL-6 and IL-23 as master regulators of tumor-associated inflammation and tumorigenesis makes them attractive targets for combinatory treatment in cancer. |
