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Lymphatic Endothelial Cell Progenitors in the Tumor Microenvironment

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Tumor Microenvironment

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1234))

Abstract

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.

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Acknowledgments

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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Authors and Affiliations

  1. Department of Medical Microbiology, Immunology, and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL, USA

    Sophia Ran & Lisa Volk-Draper

  2. Simmons Cancer Institute, Springfield, IL, USA

    Sophia Ran

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  1. Sophia Ran
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  2. Lisa Volk-Draper
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Correspondence to Sophia Ran .

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Editors and Affiliations

  1. Department of Radiology, Columbia University Medical Center, New York, NY, USA, Department of Pathology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Alexander Birbrair

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Ran, S., Volk-Draper, L. (2020). Lymphatic Endothelial Cell Progenitors in the Tumor Microenvironment. In: Birbrair, A. (eds) Tumor Microenvironment. Advances in Experimental Medicine and Biology, vol 1234. Springer, Cham. https://doi.org/10.1007/978-3-030-37184-5_7

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