Abstract 2250: Aberrant leukocyte infiltration as a trigger for tumor metastasis

Our previous studies have led to a novel hypothesis that aberrant leukocyte infiltration is a trigger for tumor invasion. Our hypothesis and supporting data have been published in multiple peer-reviewed journals. Our current studies attempted to further expand our previous observations, and to test a novel hypothesis that aberrant leukocyte infiltration may also represent a trigger for tumor metastasis. Tissue sections from human breast, prostate, cervical, and lung tumors were analyzed with multidisciplinary approaches with a panel of tumor metastasis-related biomarkers. Our study revealed that pre-invasive tumors surrounded by or immediately adjacent to leukocyte aggregates displayed a number of unique features: [1] significantly reduced expression of cell surface adhesion molecules, [2] significantly elevated blood vessels and lymphatic ducts at the intersection between the tumor core and leukocyte aggregates, [3] the presence of isolated individual tumor cells or cell clusters within the leukocyte aggregates, [4] physical attachment or fusion of tumor cell membrane and condensed chromosomes of mitotic tumor cells with leukocytes, and [5] the presence of co-joined tumor cells and leukocytes within vascular structures or lymphatic ducts. Together, our findings suggest that leukocyte infiltration may trigger tumor metastasis through three correlated mechanisms: (1) to physically disrupt the inter-cellular junctions and cell surface adhesion molecules, [2] to interfere with the mitotic process or physically drag tumor cells to different sites during their migration, and [3] to stimulate growth of vascular structures that facilitate tumor metastasis. (Supported in part by grants DAMD17-01-1-0129, DAMD17-01-1-0130, PC051308 from Congressionally Directed Medical Research Programs, grant BCTR0706983 from The Susan G. Komen Breast Cancer Foundation, and grant 2008-02 from The US Military Cancer Institute and Henry M. Jackson Foundation to Dr. Yan-gao Man, and by grant 2006CB910505 from The Ministry of Chinese Science and Technology Department to Drs. Xichen Zhang and Yan-gao Man). 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 2250.