Heterogeneity of tumor lymphangiogenesis: Progress and prospects

Lymphangiogenesis and increased expression of lymphangiogenic growth factors are associated with high rates of lymph node (LN) metastasis and with poor prognosis in some, but not all, solid tumors. In addition to its involvement in metastasis, lymphangiogenesis has been shown to have other roles in tumor pathogenesis, such as the niche function of tumor stem cells and regulatory functions of antitumor immune responses. In contrast, evidence has accumulated that tumor-induced lymphangiogenesis displays the heterogeneity in gene signature, structure, cellular origins and functional plasticity. This review summarizes the advances in the research on the heterogeneity of tumor lymphangiogenesis and discusses how it may contribute to functional complexity and multiplicity of lymphangiogenesis in tumor progression.