Abstract
Introduction: Acute ischemia/reperfusion (I/R) of normal tissues causes an inflammatory reaction initiated by binding of auto-reactive IgM antibody to an ischemia-induced self-antigen. Whether this inflammatory cascade also affects cancers - for example, after acute I/R during surgical resection or in conditions of chronic ischemia - is unclear. We examined the effect of I/R injury in three murine tumor models: B16F10 melanoma, Lewis lung carcinoma (LLC), and small intestinal adenomas of the APCmin/+ mouse.
Methods: LLC and B16F10 cell lines were implanted into the hindlimbs of C57BL/6 mice. Ischemia was induced by external tourniquet ligation of the femoral vessels. Small intestinal tumors in APC min/+ mice were subjected to ischemia by vascular clip occlusion of the superior mesenteric artery. Control animals underwent hindlimb ischemia to the non-tumor bearing hindlimb or laparotomy alone. Following graded times of ischemia and reperfusion, tumors and surrounding normal tissue were harvested for histological examination. Immunohistochemistry was performed for IgM and activated caspase-3. For hindlimb injury, mice were recovered and followed for LLC and B16F10 tumor growth.
Results: Ischemia-reperfusion causes injury of LLC and B16F10 tumors. In contrast, intestinal adenomas of APCmin/+ mice showed no signs of injury following ischemia, despite induction of necrosis and apoptosis of adjacent normal intestinal epithelium. Tumor susceptibility to ischemic injury correlated with immuno-histochemical deposition of IgM antibody. Ischemic injury of B16F10 significantly reduced tumor growth (36% volume reduction compared to control injury, p <0.05). In contrast, LLC tumor growth was significantly increased after ischemia (35% increased compared to control injury, p < 0.01)
Conclusions: The three murine tumor models examined are each affected differently by an acute I/R injury, in contrast to the conserved inflammatory cascade induced in normal tissues following ischemia. APCmin/+ adenomas evade ischemia-induced IgM binding and injury. While both LLC and B16F10 are acutely injured, the long term effects on growth are divergent. Targeted manipulation of the host inflammatory response to ischemia-reperfusion may be a method to influence tumor progression and growth.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3815.
- ©2010 American Association for Cancer Research
Volume 70, Issue 8 Supplement
