Further Insights Into the Mechanisms of Lymph Node Metastasis

Metastasis of malignant tumors arising from epithelial organs to sentinel lymph nodes has important implications for prognosis, staging, and therapeutic decision-making. Recent insights into anatomic pathways, pathogenesis, molecular interactions, and genetic factors have encouraged scientists and clinicians to develop drugs that target mechanisms of lymph node metastasis. We summarize important aspects of the vast literature that pertains to these mechanisms, focusing on five phases that implicate invasion through the epithelial basement membrane and tumor microenvironment, into initial lymphatics, and, after flow through lymphatic trunks, into the sentinel lymph node. Valuable information regarding tumor cell-directed motility, lymphangiogenesis, host cells that enhance metastasis, immune responses to tumor antigens, and tumor-induced changes in sentinel lymph node(s) provides a promising avenue for the continued development of new therapeutic approaches to prevent and treat metastasis. This article reviews these aspects by synthesizing current scientific and clinical advances and translating them for medical professionals.