journal homepage: www.elsevier.com/locate/yexcr Available online at www.sciencedirect.com Review Article Molecular mechanisms and imaging of lymphatic metastasis Steven T. Proulx, Michael Detmar n Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Wolfgang-Pauli-Str. 10, CH-8093 Zurich, Switzerland articleinformation Article Chronology: Received 18 December 2012 Accepted 2 March 2013 Keywords: Lymphatic vessels Tumor Metastasis Imaging abstract In many types of cancer, tumors metastasize through the lymphatic system to draining lymph nodes. These sentinel lymph nodes have gained increased attention as a prognostic indicator for the severity of the disease, leading to the sentinel lymph node mapping and biopsy procedure to be accepted as standard-of-care for breast cancer and melanoma. However, many limitations exist with this procedure resulting in high false negative rates. In this review we highlight the new advances in the understanding of the molecular mechanisms of lymphangiogenesis and tumor metastasis that may lead to improved strategies in the detection of the sentinel lymph nodes and therapeutic interventions to prevent further tumor spread. In addition, advances in imaging technology are allowing new approaches for anatomical mapping of lymphatic drainage patterns and molecular imaging strategies that may improve detection of metastatic tumor cells within sentinel lymph nodes. & 2013 Elsevier Inc. All rights reserved. Contents Introduction ............................................................................................. 1 Historical perspective of the lymphatic spread of cancer .......................................................... 2 Current problems with the SLN procedure ..................................................................... 2 Molecular mechanisms of LN metastasis ....................................................................... 3 Imaging of lymphatic vessels and SLNs ........................................................................ 4 Future perspectives ....................................................................................... 5 Conclusion .............................................................................................. 6 Introduction The lymphatic system plays key roles in maintaining fluid homeostasis in tissues, enabling immune responses to infection, and facilitating the uptake of dietary lipids and fat-soluble vitamins in the intestine. In many types of cancer, however, it may also act as a conduit for tumor spread, initially to draining lymph nodes (LNs) termed sentinel lymph nodes (SLNs) and eventually to distant sites. It is estimated that around 20–25% of patients that are diagnosed with melanoma will present with tumor cells in draining LNs [1,2]. In breast cancer, axillary LN involvement is found in 10–30% of patients with T1 (o2 cm) tumors, in 45% with small T2 tumors (2.1–3 cm) and in 55–70% with larger tumors (43 cm) [3]. Despite the fact that important questions 0014-4827/$ - see front matter & 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.yexcr.2013.03.009 n Corresponding author. Fax: þ41 44 633 1364. E-mail address: michael.detmar@pharma.ethz.ch (M. Detmar). EXPERIMENTAL CELL RESEARCH ] ( ]]]] ) ]]] – ]]] Please cite this article as: S.T. Proulx, M. Detmar, Molecular mechanisms and imaging of lymphatic metastasis, Exp Cell Res (2013), h ttp://dx.doi.org/10.1016/j.yexcr.2013.03.009