Acute local inflammation potentiates tumor growth in mice

Chronic inflammation in humans has been implicated in the pathogenesis of s everal types of cancer. In animals, experimentally-induced tumor growth was found to be enhanced at sites of injury. However, a direct demonstration i n vivo that an inflammatory agent applied locally at the tumor site can pro mote a switch into a highly proliferative state of tumor growth, has not ye t been documented. The present work was designed to test, in a syngeneic pr imary tumor model in mice, whether a commonly used inflammatory agent, carr ageenan, could cause acceleration of tumor growth and to investigate the ce llular mechanisms mediating such a process. Local injection of carrageenan into a tissue site containing tumor cells produced an accelerated rate of t umor growth at that site which was characterized by a decreased percentage of apoptotic cells and an increased proportion of cells at the S and G(2)/M phases of the cell cycle. The pro-tumorigenic effect of carrageenan is dos e-dependent and can be exerted at any time throughout the course of the tum or growth. Furthermore, the effect is prostaglandin-mediated since the cycl ooxygenase inhibitor indomethacin totally abrogated it. Experiments with tu mors cells in culture have shown that carrageenan actually inhibits cell pr oliferation as well as increases apoptosis. Thus, the tumor promoting effec ts of carrageenan in vivo appear to arise not from a direct effect on the t umor cells per se but rather through induction of host-dependent humoral/ce llular responses that generate increased levels of prostanoids and pro-infl ammatory cytokines that accelerate tumor growth. These data demonstrate for the first time that an acute, local inflammatory stimuli can induce accele rated tumor growth at the affected site and provide further support for a m echanism-based, anti-tumorigenic action of anti-inflammatory drugs. (C) 200 0 Elsevier Science Ireland Ltd. All rights reserved.