Cancer stem cells, lymphangiogenesis, and lymphatic metastasis

• Tumor-induced lymphangiogenesis plays an important role in promoting lymphatic metastasis.
• Several types of cells may be the origin of tumor lymphatic endothelial cells.
• CSCs closely correlate with lymphatic metastasis by multiple pathways.
• CSCs can directly convert into ECs and structures that support the tumor and its propagation.
• CSCs and lymphatic vasculature as potential therapeutic target.

Although current opinion indicates that tumor-induced lymphangiogenesis plays a key role in promoting the initial spread of malignant tumors, the mechanism that underlies lymphatic spread is not clear. The recent discovery of cancer stem cells (CSCs) in human tumors has challenged our current understanding of tumor recurrence, drug resistance, and metastasis, and opens up new research directions on how cancer cells are capable of switching from dormancy to malignancy. CSCs can be directly and indirectly involved in tumor-induced lymphangiogenesis and ultimately promote lymphatic metastasis. However, the details and the possible relationship between CSCs, lymphangiogenesis, and lymphatic metastasis remain ambiguous, and the origin of tumor lymphatic endothelial cells is controversial. Elucidation of these factors may provide useful information for future research and cancer treatment. In this article, we summarize current knowledge of CSCs, tumor-induced lymphangiogenesis, and lymphatic metastasis and attempt to find an association between key molecular and cellular mechanisms. We provide an overview of CSCs and lymphatic vasculature as potential therapeutic targets. CSC- and lymphatic vasculature-targeted therapy may bring new hope for cancer treatment.