Abstract 3815: Murine tumors demonstrate variable responses to ischemia-reperfusion injury

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