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

Sept 2012

Ran S, Montgomery KE.

Source

Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, 801 N. Rutledge, Springfield, IL 62794, USA.

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 vesselsprior 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).

NIH Public Access

Overlapping biomarkers, pathways, processes and syndromes in lymphatic development, growth and neoplasia.

Jul 15, 2012

Witte MH, Dellinger MT, Papendieck CM, Boccardo F.

Source

Department of Surgery, University of Arizona College of Medicine, 1501 N. Campbell Avenue, Tucson, AZ, 85724-5200, USA, lymph@u.arizona.edu.

Keywords:  Biomarkers – Cancer metastasis – Lymphatic development – EMT-MET – Vascular neoplasia – Lymphogenous dissemination

Abstract

Recent discoveries in molecular lymphology, developmental biology, and tumor biology in the context of long-standing concepts and observations on development, growth, and neoplasia implicate overlapping pathways, processes, and clinical manifestations in developmental disorders and cancer metastasis. Highlighted in this review are some of what is known (and speculated) about the genes, proteins, and signaling pathways and processes involved in lymphatic/blood vascular development in comparison to those involved in cancer progression and spread. Clues and conundra from clinical disordersthat mix these processes and mute them, including embryonic rests, multicentric nests of displaced cells, uncontrolled/invasive "benign" proliferation and lymphogenous/hematogenous "spread", represent a fine line between normal development and growth, dysplasia, benign and malignant neoplasia, and "metastasis". Improved understanding of these normal and pathologic processes and their underlying pathomechanisms, e.g., stem cell origin and bidirectional epithelial-mesenchymal transition, could lead to more successful approaches in classification, treatment, and even prevention of cancer and a whole host of other diseases.

Springerlink

Rare subset of diseases involving the lymphatic system

Feb 2012

New Rochelle, NY, February 8, 2012—A clinically challenging and under-studied subset of diseases affecting the lymphatic system and grouped under the disease spectrum lymphangiomatosis and Gorham's disease is the focus of a special issue of Lymphatic Research and Biology, a peer-reviewed journal published by Mary Ann Liebert, Inc.. The issue is available free online at www.liebertpub.com/lrb

Guest Editor, and Journal Associate Editor Francine Blei MD, MBA, St. Luke's Roosevelt Hospital, NY, has compiled a collection of articles that highlight the complex characteristics of these diseases, which can be localized, affect multiple sites, or be systemic, may be congenital or acquired, and may cause symptoms that range from mild to severe to life-threatening. The articles focus on current knowledge, ongoing research, and how these diseases differ from other lymphatic disorders.

"This disease spectrum affects a patient population that is small in number, but the effects of the disease(s) are devastating," says Stanley G. Rockson, MD, Editor-in-Chief of Lymphatic Research and Biology and Allan and Tina Neill Professor of Lymphatic Research and Medicine, Stanford University School of Medicine, CA. The collection of articles in this special issue, "highlights the current state of knowledge (and ignorance) in this paradoxically neglected area of lymphatic health and disease."

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Lymphatic Research and Biology is an authoritative peer-reviewed journal published quarterly in print and online that delivers the latest developments and advances in lymphatic biology and pathology from the world's leading biomedical investigators. Topics covered include vasculogenesis and angiogenesis, genetics of lymphatic disorders, human lymphatic disease, tumor biology and metastasis, pharmacology, lymphatic imaging, and inflammation, infection, and autoimmune disease. Complete tables of content and a sample issue may be viewed online at www.liebertpub.com/lrb

Mary Ann Liebert, Inc. is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including Cancer Biotherapy and Radiopharmaceuticals and DNA and Cell Biology. Its biotechnology trade magazine, Genetic Engineering & Biotechnology News (GEN), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's 70 journals, books, and newsmagazines is available at www.liebertpub.com

Mary Ann Liebert, Inc. 140 Huguenot St., New Rochelle, NY 10801-5215 www.liebertpub.com
Phone: (914) 740-2100 (800) M-LIEBERT Fax: (914) 740-2101

Lymphatic involvement in lymphangioleiomyomatosis.

Lymphatic involvement in lymphangioleiomyomatosis.

Ann N Y Acad Sci. 2008 May
Glasgow CG, Taveira-Dasilva AM, Darling TN, Moss J.
PhD., Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bldg. 10, Rm. 6D03 MSC 1590, Bethesda, MD 20892-1590. mossj@nhlbi.nih.gov.

Lymphangioleiomyomatosis (LAM) is a rare, multisystem disease affecting primarily premenopausal women. The disease is characterized by cystic lung disease, at times leading to respiratory compromise, abdominal tumors (in particular, renal angiomyolipomas), and involvement of the axial lymphatics (e.g., adenopathy, lymphangioleiomyomas).

Disease results from the proliferation of neoplastic cells (LAM cells), which, in many cases, have a smooth muscle cell phenotype, express melanoma antigens, and have mutations in one of the tuberous sclerosis complex genes (TSC1 or TSC2). In the lung, LAM cells found in the vicinity of cysts are, at times, localized in nodules and may be responsible for cyst formation through the production of proteases.

Lymphatic channels, expressing characteristic lymphatic endothelial cell markers, are found within the LAM lung nodules. LAM cells may also be localized within the walls of the axial lymphatics, and, in some cases, penetrate the wall and proliferate in the surrounding adipose tissue. Consistent with extensive lymphatic involvement in LAM, the serum concentration of VEGF-D, a lymphangiogenic factor, is higher in LAM patients than in healthy volunteers.

Annals of the New York Academy of Sciences