Presence of bone marrow–derived circulating progenitor endothelial cells in the newly formed lymphatic vessels

Religa, Piotr; Cao, Renhai; Björndahl, Meit A.; Zhou, Zhongjun; Zhu, Zhenping; Cao, Yihai

doi:10.1182/blood-2005-01-0226

Cited by 124 publications

(153 citation statements)

References 30 publications

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“…These cells are functionally nonadherent endothelial precursor cells that can differentiate into mature adherent VEGFR-3 þ endothelial cells in the presence of vascular growth factors. In a corneal lymphangiogenesis model of irradiated mice reconstituted with donor BM cells, both CD34 þ /VEGFR-2 þ cells and CD34 þ / VEGF-C (plasma) Not increased compared to controls Strauss et al (2005) VEGFR-3 þ cells were found to be incorporated into the newly formed lymphatic vessels (Religa et al, 2005). A second population of candidate LECPs has now been identified.…”

Section: Other Markersmentioning

confidence: 99%

First international consensus on the methodology of lymphangiogenesis quantification in solid human tumours

et al. 2006

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The lymphatic system is the primary pathway of metastasis for most human cancers. Recent research efforts in studying lymphangiogenesis have suggested the existence of a relationship between lymphatic vessel density and patient survival. However, current methodology of lymphangiogenesis quantification is still characterised by high intra-and interobserver variability. For the amount of lymphatic vessels in a tumour to be a clinically useful parameter, a reliable quantification technique needs to be developed. With this consensus report, we therefore would like to initiate discussion on the standardisation of the immunohistochemical method for lymphangiogenesis assessment. Metastasis is the leading cause of cancer mortality. Metastatic cancer cells can escape from their site of origin and spread to distant organs through invasion of the vascular system and/or the lymphatic system. Tumour vascularisation is widely accepted as a bona fide indicator of tumour growth, metastases and patient survival. In 1996, Peter Vermeulen et al (1996) published a first international consensus on the methodology and criteria of the evaluation of angiogenesis quantification in solid tumours and 5 years later, a second consensus report, in which new concepts and mechanisms of tumour vascularisation were integrated, appeared (Vermeulen et al, 2002). Both reports were aimed at improving the standardisation of angiogenesis quantification in order to allow intratumourous microvessel density to be applied as a prognostic indicator and, moreover, as a reliable predictor of the risk of malignant transformation of premalignant lesions and of response to cancer treatment. Contrary to angiogenesis, the de novo formation of lymphatic vessels or lymphangiogenesis and its role in promoting the metastatic spread of tumour cells has only recently become a focal point of cancer research with an increasing number of studies showing a relationship between patient survival and lymphatic density in different tumour types. In order to confirm the potential prognostic value of lymphangiogenesis in patients with cancer, a quantification method that is characterised by a low intra-and interobserver variability needs to be developed. In this first consensus report, we would like to provide an overview of current concepts of the lymphatic vasculature and its regulating factors and propose guidelines for the estimation of the ongoing lymphangiogenesis in solid human tumour sections.

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Section: Other Markersmentioning

confidence: 99%

First international consensus on the methodology of lymphangiogenesis quantification in solid human tumours

et al. 2006

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“…Immunohistochemical staining of whole-mount tissue samples was performed according to our previously published methods [33][34][35][36][37][38] . Treated and non-treated tumour tissues were fixed with 4% PFA overnight and cut into small pieces.…”

Section: Measurement Of Ctcs Using Facsmentioning

confidence: 99%

Tumour PDGF-BB expression levels determine dual effects of anti-PDGF drugs on vascular remodelling and metastasis

et al. 2013

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Anti-platelet-derived growth factor (PDGF) drugs are routinely used in front-line therapy for the treatment of various cancers, but the molecular mechanism underlying their dosedependent impact on vascular remodelling remains poorly understood. Here we show that anti-PDGF drugs significantly inhibit tumour growth and metastasis in high PDGF-BB-producing tumours by preventing pericyte loss and vascular permeability, whereas they promote tumour cell dissemination and metastasis in PDGF-BB-low-producing or PDGF-BB-negative tumours by ablating pericytes from tumour vessels. We show that this opposing effect is due to PDGF-b signalling in pericytes. Persistent exposure of pericytes to PDGF-BB markedly downregulates PDGF-b and inactivation of the PDGF-b signalling decreases integrin a1b1 levels, which impairs pericyte adhesion to extracellular matrix components in blood vessels. Our data suggest that tumour PDGF-BB levels may serve as a biomarker for selection of tumour-bearing hosts for anti-PDGF therapy and unsupervised use of anti-PDGF drugs could potentially promote tumour invasion and metastasis.

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“…In mice subcutaneously transplanted with B16F1 melanoma and Lewis lung carcinoma and previously transplanted with genetically labeled bone marrow, no integration of bone marrow-derived cells into tumor-associated lymphatic vessels has been observed (He et al 2004). In contrast, contribution of bone marrow cells has been observed in subcutaneous T241 fibrosarcoma tumors and in the genetic Apc Min/þ model of intestinal adenoma (Religa et al 2005;Jiang et al 2008). In the transgenic Rip1Tag2 mouse model of pancreatic b-cell carcinogenesis and in subcutaneously grown TRAMP-C1 prostate adenocarcinoma, a combination of adoptive bone marrow transfer and genetic lineage tracing experiments has revealed that bone marrow-derived cells of the myeloid lineage integrate into tumorassociated lymphatic vessels ).…”

Section: Myeloid-endothelial Plasticity In Pathological Inflammation mentioning

confidence: 93%

“…Direct evidence for de novo lymphatic vessel formation is provided by the ex vivo culturing of previously unchallenged, isolated corneas (not containing any endothelial cells but CD11b þ myeloid cells), which under IL1b stimulation develop LYVE-1 þ /CD31 þ structures in absence of any connected endothelial structure. This study and a second one, placing FGF2-loaded micropellets in corneas, also show integration of bone marrow-derived cells into newly formed lymphatic vessels in the cornea, illustrating the rapid mobilization of bone marrow cells and recruitment to the cornea on inflammation (Religa et al 2005).…”

Section: Myeloid-endothelial Plasticity In Pathological Inflammation mentioning

confidence: 97%

Myeloid Cells and Lymphangiogenesis

Zumsteg

2012

Cold Spring Harbor Perspectives in Medicine

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The lymphatic vascular system and the hematopoietic system are intimately connected in ontogeny and in physiology. During embryonic development, mammalian species derive a first lymphatic vascular plexus from the previously formed anterior cardinal vein, whereas birds and amphibians have a lymphatic vascular system of dual origin, composed of lymphatic endothelial cells (LECs) of venous origin combined with LECs derived from mesenchymal lymphangioblasts. The contribution of hematopoietic cells as building blocks of nascent lymphatic structures in mammals is still under debate. In contrast, the importance of myeloid cells to direct lymphatic vessel growth and function postnatally has been experimentally shown. For example, myeloid cells communicate with LECs via paracrine factors or cell -cell contacts, and they also can acquire lymphatic endothelial morphology and marker gene expression, a process reminiscent of developmental vasculogenesis. Here, we present an overview of the current understanding of how lymphatic vessels and the hematopoietic system, in particular myeloid cells, interact during embryonic development, in normal organ physiology, and in disease.

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Presence of bone marrow–derived circulating progenitor endothelial cells in the newly formed lymphatic vessels

Cited by 124 publications

References 30 publications

First international consensus on the methodology of lymphangiogenesis quantification in solid human tumours

First international consensus on the methodology of lymphangiogenesis quantification in solid human tumours

Tumour PDGF-BB expression levels determine dual effects of anti-PDGF drugs on vascular remodelling and metastasis

Myeloid Cells and Lymphangiogenesis

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