The Sialomucin CD34 Is a Marker of Lymphatic Endothelial Cells in Human Tumors

Department of Vascular Biology and Angiogenesis Research, Tumor Biology Center, Breisacher Strasse 117, D-79106 Freiburg, Germany.
American Journal Of Pathology (Impact Factor: 4.59). 04/2006; 168(3):1045-53. DOI: 10.2353/ajpath.2006.050554
Source: PubMed


The mechanisms of lymphangiogenesis have been increasingly understood in recent years. Yet, the contribution of lymphangiogenesis versus lymphatic cooption in human tumors and the functionality of tumor lymphatics are still controversial. Furthermore, despite the identification of lymphatic endothelial cell (LEC) markers such as Prox1, podoplanin, LYVE-1, and VEGFR-3, no activation marker for tumor-associated LECs has been identified. Applying double-staining techniques with established LEC markers, we have screened endothelial cell differentiation antigens for their expression in LECs. These experiments identified the sialomucin CD34 as being exclusively expressed by LECs in human tumors but not in corresponding normal tissues. CD34 is expressed by LYVE-1(+)/podoplanin(+)/Prox1(+) tumor-associated LECs in colon, breast, lung, and skin tumors. More than 60% of analyzed tumors contained detectable intratumoral lymphatics. Of these, more than 80% showed complete co-localization of CD34 with LEC markers. In contrast, LECs in all analyzed normal organs did not express CD34. Corresponding analyses of experimental tumors revealed that mouse tumor-associated LECs do not express CD34. Taken together, these experiments identify CD34 as the first differentially expressed LEC antigen that is selectively expressed by tumor-associated LECs. The data warrant further exploration of CD34 in tumor-associated LECs as a prognostic tumor marker.

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    • "Vascular endothelial (VE)-cadherin/CD144 is a specific adhesion molecule of ECs and the major component of adherent junctions [15], [16]. Sialomucin/CD34 is mainly expressed by hematopoietic progenitor cells and by ECs from blood vessels, but not by ECs from lymphatic vessels [17]–[19]. ICAM-1/CD54 is expressed constitutively at low levels on vascular ECs and also on leukocytes [20]. ICAM-2/CD102 is expressed constitutively on lymphocytes, monocytes, platelets and ECs. "
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    ABSTRACT: Comparative analysis of the cellular biology of the microvasculature in different tissues requires the availability of viable primary endothelial cells (ECs). This study describes a novel method to isolate primary ECs from healthy organs, repair blastemas and tumors as examples of non-proliferating and proliferating benign and malignant tissues and their functional characterization. Single cell suspensions from hearts, lungs, repair blastemas and tumors were incubated consecutively with an anti-CD31 antibody and magnetic micro-beads, coupled to a derivative of biotin and streptavidin, respectively. Following magnetic bead separation, CD31-positive ECs were released by biotin-streptavidin competition. In the absence of micro-beads, ECs became adherent to plastic surfaces. ECs from proliferating repair blastemas and tumors were larger and exhibited higher expression densities of CD31, CD105 and CD102 compared to those from non-proliferating normal tissues such as heart and lung. The expression density of CD34 was particularly high in tumor-derived ECs, and that of CD54 and CD144 in ECs of repair blastemas. Functionally, ECs of non-proliferating and proliferating tissues differed in their capacity to form tubes in matrigel and to align under flow conditions. This method provides a powerful tool to generate high yields of viable, primary ECs of different origins. The results suggest that an altered expression of adhesion molecules on ECs in proliferating tissues contribute to loss of EC function that might cause a chaotic tumor vasculature.
    PLoS ONE 03/2014; 9(3):e91808. DOI:10.1371/journal.pone.0091808 · 3.23 Impact Factor
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    • "Vascularization was determined on the basis of staining of CD34, which is profoundly present on the endothelium of arteries, veins and capillaries and is widely used as an endothelial marker. CD34 has also been encountered in lymphatic endothelial cells of various tumours, but was absent in the lymphatic endothelial cells of unaffected tissues (Fiedler et al., 2006). In addition, Rogers et al. (2008) concluded that endometrial lymphatic endothelial cells were negative for CD34. "
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    Human Reproduction 10/2008; 24(1):185-97. DOI:10.1093/humrep/den296 · 4.57 Impact Factor
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    • "Just as tumour vasculature has a markedly different phenotype from normal vessels, so it is highly likely that tumour lymphatic vessels will differ from normal and gene array studies on lymphatic endothelium isolated from tumours will be of major interest to help develop new markers relevant to tumour therapy and outcome. Fiedler et al (2006) very recently reported that the CD34 protein, a recognised vascular endothelial marker, is selectively expressed in tumour-associated LECs and not in resting organ LECs. The expression of CD34 by tumour-associated LECs was identified in colon cancer, breast cancer, lung cancer and melanoma. "
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