Lymphatic Endothelial Cell Progenitors in the Tumor Microenvironment

  • Sophia RanEmail author
  • Lisa Volk-Draper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1234)


Tumor lymphatics play a key role in cancer progression as they are solely responsible for transporting malignant cells to regional lymph nodes (LNs), a process that precedes and promotes systemic lethal spread. It is broadly accepted that tumor lymphatic sprouting is induced mainly by soluble factors derived from tumor-associated macrophages (TAMs) and malignant cells. However, emerging evidence strongly suggests that a subset of TAMs, myeloid-lymphatic endothelial cell progenitors (M-LECP), also contribute to the expansion of lymphatics through both secretion of paracrine factors and a self-autonomous mode. M-LECP are derived from bone marrow (BM) precursors of the monocyte-macrophage lineage and characterized by unique co-expression of markers identifying lymphatic endothelial cells (LEC), stem cells, M2-type macrophages, and myeloid-derived immunosuppressive cells. This review describes current evidence for the origin of M-LECP in the bone marrow, their recruitment tumors and intratumoral trafficking, similarities to other TAM subsets, and mechanisms promoting tumor lymphatics. We also describe M-LECP integration into preexisting lymphatic vessels and discuss potential mechanisms and significance of this event. We conclude that improved mechanistic understanding of M-LECP functions within the tumor environment may lead to new therapeutic approaches to suppress tumor lymphangiogenesis and metastasis to lymph nodes.


Bone marrow Breast cancer Endothelial cell lineage development Hematopoietic stem cell differentiation Inflammation Lymphangiogenesis Lymphatic metastasis Lymphatic endothelial progenitors M2-type macrophages Myeloid-derived pro-vascular progenitors Myeloid-derived suppressor cells Tumor macrophages Toll-like receptor 4 Tumor microenvironment Vessel formation 



The authors are grateful to Susan Ryherd for critical review and editing. This manuscript was supported by a grant # R01CA199649 awarded to Sophia Ran by the National Institutes of Health and a Team Science Grant from Simmons Cancer Institute funded by proceeds of the Denim and Diamonds charity event.


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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of Medical Microbiology, Immunology, and Cell BiologySouthern Illinois University School of MedicineSpringfieldUSA
  2. 2.Simmons Cancer InstituteSpringfieldUSA

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