Metastasis to the omentum, a fatty tissue that drapes from the stomach, commonly occurs in older women with ovarian cancer and causes substantial pain and bowel obstruction. It is difficult to surgically remove the entire omentum and there are no effective strategies that minimize the risk of colonization of preserved omental tissues by occult or hidden cancer cells. Studies of young and aged mice strongly implicate that aging increases the propensity of the omentum for metastasis, but the underlying mechanisms are unclear. The goal of this study is to identify how aging increases the propensity of the omentum for metastasis and develop strategies that decrease this propensity in older femal...

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Metastasis to the omentum, a fatty tissue that drapes from the stomach, commonly occurs in older women with ovarian cancer and causes substantial pain and bowel obstruction. It is difficult to surgically remove the entire omentum and there are no effective strategies that minimize the risk of colonization of preserved omental tissues by occult or hidden cancer cells. Studies of young and aged mice strongly implicate that aging increases the propensity of the omentum for metastasis, but the underlying mechanisms are unclear. The goal of this study is to identify how aging increases the propensity of the omentum for metastasis and develop strategies that decrease this propensity in older females. We hypothesize that the heightened propensity of the omentum for metastasis in aged females stems from age-related increases in innate-like B cells with immunosuppressive properties, and that inhibiting mobilization of these B cells to the omentum decreases its propensity for metastasis in aged females. In this study, we will firstly determine whether the heightened propensity of the omentum for metastasis in aged females stems from increases in innate-like B cells. Secondly, we will determine whether mobilization of immunosuppressive B cells to the omentum is increased in aged females, thereby increasing the propensity of the omentum for metastasis. Thirdly, we will develop a strategy to suppress mobilization of immunosuppressive B cells to the omentum in aged females. These aims will be accomplished by a combination of approaches that utilize genetically modified mice, clinical specimens of human omentum, molecular analysis, and pharmacologic inhibition. If successful, our study will yield new, fundamental insights that explain why aging increases the propensity of the omentum for metastasis and valuable insights into minimizing the risk of omental metastasis by occult ovarian cancer cells in older women.

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