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Cancers 2012, 4(3), 618-657; doi:10.3390/cancers4030618
Review

Macrophage-Mediated Lymphangiogenesis: The Emerging Role of Macrophages as Lymphatic Endothelial Progenitors

*  and
Received: 2 May 2012; in revised form: 15 June 2012 / Accepted: 20 June 2012 / Published: 27 June 2012
(This article belongs to the Special Issue Tumor Stroma)
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Abstract: It is widely accepted that macrophages and other inflammatory cells support tumor progression and metastasis. During early stages of neoplastic development, tumor-infiltrating macrophages (TAMs) mount an immune response against transformed cells. Frequently, however, cancer cells escape the immune surveillance, an event that is accompanied by macrophage transition from an anti-tumor to a pro-tumorigenic type. The latter is characterized by high expression of factors that activate endothelial cells, suppress immune response, degrade extracellular matrix, and promote tumor growth. Cumulatively, these products of TAMs promote tumor expansion and growth of both blood and lymphatic vessels that facilitate metastatic spread. Breast cancers and other epithelial malignancies induce the formation of new lymphatic vessels (i.e., lymphangiogenesis) that leads to lymphatic and subsequently, to distant metastasis. Both experimental and clinical studies have shown that TAMs significantly promote tumor lymphangiogenesis through paracrine and cell autonomous modes. The paracrine effect consists of the expression of a variety of pro-lymphangiogenic factors that activate the preexisting lymphatic vessels. The evidence for cell-autonomous contribution is based on the observed tumor mobilization of macrophage-derived lymphatic endothelial cell progenitors (M-LECP) that integrate into lymphatic vessels prior to sprouting. This review will summarize the current knowledge of macrophage-dependent growth of new lymphatic vessels with specific emphasis on an emerging role of macrophages as lymphatic endothelial cell progenitors (M-LECP).
Keywords: lymphatic endothelial cell progenitors; tumor associated macrophages; lymphangiogenesis; lymphvasculogenesis; lymphatic metastasis lymphatic endothelial cell progenitors; tumor associated macrophages; lymphangiogenesis; lymphvasculogenesis; lymphatic metastasis
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Ran, S.; Montgomery, K.E. Macrophage-Mediated Lymphangiogenesis: The Emerging Role of Macrophages as Lymphatic Endothelial Progenitors. Cancers 2012, 4, 618-657.

AMA Style

Ran S, Montgomery KE. Macrophage-Mediated Lymphangiogenesis: The Emerging Role of Macrophages as Lymphatic Endothelial Progenitors. Cancers. 2012; 4(3):618-657.

Chicago/Turabian Style

Ran, Sophia; Montgomery, Kyle E. 2012. "Macrophage-Mediated Lymphangiogenesis: The Emerging Role of Macrophages as Lymphatic Endothelial Progenitors." Cancers 4, no. 3: 618-657.


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