Acute local inflammation potentiates tumor growth in mice.
Chronic inflammation in humans has been implicated in the pathogenesis of several types of cancer. In animals, experimentally-induced tumor growth was found to be enhanced at sites of injury. However, a direct demonstration in vivo that an inflammatory agent applied locally at the tumor site can promote a switch into a highly proliferative state of tumor growth, has not yet been documented. The present work was designed to test, in a syngeneic primary tumor model in mice, whether a commonly used inflammatory agent, carrageenan, could cause acceleration of tumor growth and to investigate the cellular mechanisms mediating such a process. Local injection of carrageenan into a tissue site containing tumor cells produced an accelerated rate of tumor growth at that site which was characterized by a decreased percentage of apoptotic cells and an increased proportion of cells at the S and G2/M phases of the cell cycle. The pro-tumorigenic effect of carrageenan is dose-dependent and can be exerted at any time throughout the course of the tumor growth. Furthermore, the effect is prostaglandin-mediated since the cyclooxygenase inhibitor indomethacin totally abrogated it. Experiments with tumors cells in culture have shown that carrageenan actually inhibits cell proliferation as well as increases apoptosis. Thus, the tumor promoting effects of carrageenan in vivo appear to arise not from a direct effect on the tumor cells per se but rather through induction of host-dependent humoral/cellular responses that generate increased levels of prostanoids and pro-inflammatory cytokines that accelerate tumor growth. These data demonstrate for the first time that an acute, local inflammatory stimuli can induce accelerated tumor growth at the affected site and provide further support for a mechanism-based, anti-tumorigenic action of anti-inflammatory drugs.
Raz
A
A
Department of Biochemistry, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Israel. amiraz@post.tau.ac.il
Levine
G
G
Khomiak
Y
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018827:Carcinoma, Lewis Lung / Q000473:pathology*; D002351:Carrageenan / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000473:pathology*; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured
D002351:Carrageenan