Tuck1,2,4, Ann F. Chambers1,2,4, John D. Lewis1,3,4 1 London Regional Cancer Program, LHSC, London, ON, Canada, 2 Pathology, University of Western Ontario, London, ON, Canada, 3 Surgery, University of Western Ontario, London, ON, Canada, 4 Oncology, University
of Western Ontario, London, ON, Canada Maspin (Serpin B5) is a tumor suppressor that promotes apoptosis and inhibits angiogenesis, tumor formation and metastasis of breast cancer. A number of early clinical studies found that increased levels of Maspin were associated with a worse prognosis, while others found decreased Maspin expression in the primary tumor and undetectable levels in metastases. In subsequent studies, it was found that nuclear localization correlated with a well-differentiated phenotype, chemo-responsiveness and improved survival. These clinical
data suggest that the anti-metastatic selleckchem activity of Maspin resides in the nucleus. However, the exact mechanism by which Maspin Wnt inhibitor prevents metastasis is unknown. To investigate this, we assessed the effect of Maspin over-expression in two human cancer cell lines that do not normally express Maspin; MDA-MB-231-luc-D3H2LN, a lymph node-tropic breast cancer cell line, compared to HEp3, a (head and neck) squamous cell carcinoma. Over-expression of Maspin inhibited invasion of both cell lines in the Boyden chamber assay, but did not inhibit cell spreading of cells grown in Matrigel. In vivo, it was observed that while Maspin expression did not affect migration velocity, there was a 40% decrease in average displacement compared to control cells. Over-expression of Maspin in both cell lines resulted in diminished lung metastasis using a spontaneous metastasis assay in chick embryos. However, in an experimental metastasis model, the ability to seed secondary sites and establish metastases was comparable to that of vector control cells. These data indicate that Maspin expression inhibits an early step in metastasis from a primary tumor. Funded by a Post doctoral Fellowship Award from the Terry Fox Foundation (to BG) and grant Casein kinase 1 #016506 from the Canadian Breast Cancer Research Alliance (to ABT, AFC, JDL).
Grant #018176 from NCIC/Terry Fox Foundation (to JDL). Poster No. 77 Bone Marrow-derived Cells are Critical Mediators of Tumor Lymphangiogenesis and Promote Lymph Node Metastasis Selena Granitto 1 , Hannah Lederman2, Till-Martin Theilen4, Jared Wels1, John Lawrence2, Rosandra Kaplan2,3, David Lyden1,2,3 1 Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY, USA, 2 Department of Pediatric Hematology-Oncology, Weill Cornell Medical College, New York, NY, USA, 3 Department of Pediatrics, Memorial Sloan-Kettering Cancer VX-680 molecular weight Center, New York, NY, USA, 4 Department of Pediatric Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA Tumor lymph vessels are a key component required for tumor growth and metastatic progression.