Article The Rockefeller University Press $30.00

Metastasis of tumor cells to the regional lymph nodes is one of the key indicators of tumor ag-gressiveness. Lymph node status is a powerful predictor of patient survival and it is one of the key parameters used for determining the stage of disease progression and treatment options (Greene et al., 2006; Morton et al., 2006). Despite the paramount importance of lymph node sta-tus for the patient outcome, the mechanisms by which tumor cells are recruited to the lymph nodes are poorly understood. According to the current paradigm, once tumor cells gain access to the lymphatic vessels, they are carried with the flow of lymph into the sentinel lymph nodes where they subsequently reside. Entry of tumor cells into the lymphatics has been thought to occur randomly, as a conse-quence of tumor cell invasion through tissue. However, recent findings indicate that tumor cells are guided into the lymphatic vessels by chemokines produced by lymphatic endothe-lium (Ben-Baruch, 2008; Das and Skobe, 2008). The CCL21-CCR7 ligand-receptor pair is thought to play a central role in directing tumor cells to the lymph nodes. CCL21 is constitutively expressed by the lymphatic vessels (Gunn et al., 1998; Podgrabinska et al., 2002; Kerjaschki et al., 2004; Shields et al., 2007a), and its receptor CCR7 is expressed by melanoma and breast can-cer cells (Müller et al., 2001; Houshmand and Zlotnik, 2003). Overexpression of CCR7 in melanoma has been shown to facilitate tumor metastasis to the lymph nodes in a mouse model (Wiley et al., 2001) and clinical studies have confirmed the association between CCR