The Lyons laboratory focuses on mechanisms of lymphatic mediated metastasis of breast cancer. Specifically, we utilize mouse models of breast cancer to investigate developmentally regulated programs of inflammation and lymphangiogenesis that are utilized in the adult mammary gland and may be hijacked by breast tumor cells. The results of these translational studies have the potential to instruct therapy aimed at prevention of breast cancer metastasis.
In the past decade, postpartum breast cancers have emerged as a highly metastatic subset of young women’s breast cancer(1, 2). While definitions of postpartum breast cancer vary, increased metastasis and decreased survival is consistently observed in women who are diagnosed with breast cancer after pregnancy(3-6). Our recently published studies indicate that women diagnosed with breast cancer within 2-3 years postpartum have increased incidence of lymph node metastasis and increased lymphatic vessel density in the tumor microenvironment. Further, in animal models we have shown that pro-inflammatory enzyme cyclooxygenase-2 is a driver of metastasis as well as lymphangiogenesis in the tumor microenvironment(7, 8). Importantly, specific inhibitors of COX-2 block lymphangiogenesis in both normal mammary tissue and in the tumor microenvironment, suggesting that anti-COX-2 therapies may inhibit metastasis by blocking lymphangiogenesis(8).
Current studies in the Lyons lab focus on the mechanisms that cells of the normal mammary tissue, postpartum tumor cells, as well as breast cancer cells in general, utilize to increase the number of lymphatic vessels. In addition, we also wish to determine whether the process of tumor cell recruitment and invasion of lymphatic structures is dependent on COX-2 and other known pro-lymphangiogenic factors. The ultimate goal of our work is to identify targets for therapeutic intervention and chemoprevention in young women at risk for breast cancer and breast cancer metastasis and to advance these targets to clinical trail.
Schedin P. Pregnancy-associated breast cancer and metastasis. Nat Rev Cancer.2006;6(4):281-91.
Lyons TR, Schedin PJ, and Borges VF. Pregnancy and breast cancer: when they collide. J Mammary Gland Biol Neoplasia. 2009;14(2):87-98.
Callihan EB, Gao D, Jindal S, Lyons TR, Manthey E, Edgerton S, Urquhart A, Schedin P, and Borges VF. Postpartum diagnosis demonstrates a high risk for metastasis and merits an expanded definition of pregnancy-associated breast cancer. Breast Cancer Res Treat. 2013;138(2):549-59.
Stensheim H, Moller B, van Dijk T, and Fossa SD. Cause-specific survival for women diagnosed with cancer during pregnancy or lactation: a registry-based cohort study. J Clin Oncol. 2009;27(1):45-51.
Johansson AL, Andersson TM, Hsieh CC, Cnattingius S, and Lambe M. Increased Mortality in Women with Breast Cancer Detected during Pregnancy and Different Periods Postpartum. Cancer Epidemiol Biomarkers Prev.2011;20(9):1865-72.
Borges VF, and Schedin PJ. Pregnancy-associated breast cancer: An entity needing refinement of the definition. Cancer. 2011.
Lyons TR, O'Brien J, Borges VF, Conklin MW, Keely PJ, Eliceiri KW, Marusyk A, Tan AC, and Schedin P. Postpartum mammary gland involution drives progression of ductal carcinoma in situ through collagen and COX-2. Nat Med.2011;17(9):1109-15.
Lyons TR, Borges VF, Betts CB, Guo Q, Kapoor P, Martinson HA, Jindal S, and Schedin P. Cyclooxygenase-2-dependent lymphangiogenesis promotes nodal metastasis of postpartum breast cancer. The Journal of clinical investigation.2014.
Traci Lyons, PhD
Lyndsey Crump, MS
Alexander Stoller, BA
Professional Research Assistant
Sarah Tarullo, MS
Taylor Wallace, BA
Veronica Wessells, BS
Professional Research Assistant