Citations of BMS150
Calcium Oxalate Crystal Adherence to Hyaluronan-, Osteopontin-, and CD44-Expressing Injured/Regenerating Tubular Epithelial Cells in Rat Kidneys
Asselman,Marino; Verhulst,Anja; de Broe,Marc E.; Verkoelen,Carl F.
Journal of the American Society of Nephrology 2003;14:3155-3166.
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Abstract
ABSTRACT. Retention of crystals in the kidney is an essential early step in renal stone formation. Studies with renal tubular cells in culture indicate that hyaluronan (HA) and osteopontin (OPN) and their mutual cell surface receptor CD44 play an important role in calcium oxalate (CaOx) crystal binding during wound healing. This concept was investigated in vivo by treating rats for 1, 4, and 8 d with ethylene glycol (0.5 and 0.75%) in their drinking water to induce renal tubular cell damage and CaOx crystalluria. Tubular injury was morphologically scored on periodic acid-Schiff-stained renal tissue sections and tissue repair assessed by immunohistochemical staining for proliferating cell nuclear antigen. CaOx crystals were visualized in periodic acid-Schiff-stained sections by polarized light microscopy, and renal calcium deposits were quantified with von Kossa staining. HA was visualized with HA-binding protein and OPN and CD44 immunohistochemically with specific antibodies and quantified with an image analyzer system. Already after 1 d of treatment, both concentrations of ethylene glycol induced hyperoxaluria and CaOx crystalluria. At this point, there was neither tubular injury nor crystal retention in the kidney, and expression of HA, OPN, and CD44 was comparable to untreated controls. After 4 and 8 d of ethylene glycol, however, intratubular crystals were found adhered to injured/regenerating (proliferating cell nuclear antigen positive) tubular epithelial cells, expressing HA, OPN, and CD44 at their luminal membrane. In conclusion, the expression of HA, OPN, and CD44 by injured/regenerating tubular cells seems to play a role in retention of crystals in the rat kidney
3
Molecular Markers of Micrometastasis in OCSCCA
Germani,Ross M.; Civantos,Francisco J.; Franzmann,Elizabeth J.
Otolaryngology - Head and Neck Surgery 2008;139:P91-P92.
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1805
CD44 and hyaluronate expression in follicular mucinosis
Kaya,Gürkan; Augsburger,Eric; Chavaz,Pierre; Saurat,Jean Hilaire
Journal of Cutaneous Pathology 2006;33:227-230.
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Abstract
Background: CD44 is a membrane glycoprotein and the major cell-surface receptor of hyaluronate (HA). Lack of CD44 expression in mouse epidermis leads to an abnormal HA accumulation in the dermis, indicating an important role of CD44 in local HA metabolism. Decrease of epidermal CD44 expression in patients of lichen sclerosus et atrophicus is potentially responsible for dermal deposition of HA in this disease. Stromal HA accumulation is associated with decreased or lost expression of CD44 in perifollicular solitary cutaneous myxoma, myxoid dermatofibroma, and dermatofibrosarcoma protuberans. Methods: We examined the expression of CD44 and HA in the skin biopsy specimens of 10 patients with follicular mucinosis by using CD44-specific antibodies and biotinylated HA-binding protein (HABP), respectively. Results: No difference of CD44 expression was observed in the follicular keratinocytes when compared with those of unaffected interfollicular epidermis. The follicular zones of mucin deposition were strongly positive for HA. A weak interkeratinocyte staining for HA was also observed in the interfollicular epidermis. However, HABP staining revealed a stronger reactivity in the follicular keratinocytes surrounding the mucin-accumulated areas compared to the interfollicular keratinocytes. Conclusion: Our results suggest an active secretion of HA by follicular cells in follicular mucinosis. Kaya G, Augsburger E, Chavaz P, Saurat J-H. CD44 and hyaluronate expression in follicular mucinosis
1372
Decrease in Epidermal CD44 Expression as a Potential Mechanism for Abnormal Hyaluronate Accumulation in Superficial Dermis in Lichen Sclerosus et Atrophicus
Kaya,Gürkan; Augsburger,Eric; Stamenkovic,Ivan; Saurat,Jean Hilaire
J Investig Dermatol 2000;115:1054-1058.
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Abstract
CD44 is a polymorphic integral membrane glycoprotein that serves as the principal cell surface receptor for hyaluronate, the major component of the extracellular matrix. CD44 is abundantly found in the skin and functions as a cell adhesion molecule. In a recent study we have observed a massive dermal accumulation of hyaluronate as a result of the in vivo selective suppression of CD44 in keratinocytes in mice expressing a keratin 5 promoter-driven CD44 anti-sense transgene. As the histologic features of the dorsal skin of these transgenic mice display some similarities to those of the skin lesions of lichen sclerosus et atrophicus, we explored the nature of the material accumulated in the dermis of genital and extragenital lesions of 14 patients with lichen sclerosus et atrophicus by Alcian Blue and human CD44 receptor globulin stainings, as well as the epidermal expression of CD44 protein and mRNA by immunohistochemistry and in situ hybridization. In this study we provide evidence that hyaluronate is accumulated in the superficial dermis of lichen sclerosus et atrophicus lesions, in particular by the use of human CD44 receptor globulin staining, which binds specifically to hyaluronate. In addition we show that the protein and mRNA expression of CD44 in the epidermis of the involved lichen sclerosus et atrophicus skin from genital and extragenital areas is significantly decreased, and in some cases completely lost. In contrast, keratinocyte CD44 expression was un-altered in the skin lesions of lupus erythematosus, scleroderma and reticular erythematous mucinosis, despite the presence of a mucinous material in the dermis. These results suggest that a decrease in CD44 in the keratinocytes may be correlated with an abnormal dermal accumulation of hyaluronate in the lesions of lichen sclerosus et atrophicus, and may play a pathogenetic role in this disease.
1208
Expression of the Hyaluronan Receptor, CD44S, in Epithelial Ovarian Cancer Is an Independent Predictor of Survival
Kayastha,Sanjiv; N.,Andrew; M.,Freedman; Piver,Steven; Mukkamalla,Jhansi; Romero-Guittierez,Maritza; Werness,Bruce A.
Clinical Cancer Research 1999;5:1073-1076.
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Abstract
Most ovarian carcinomas present at advanced stage, principally as the result of dissemination to peritoneal sites. Standard CD44 (CD44S) is the principal receptor for hyaluronic acid, and in vitro and animal studies have suggested that the attachment of ovarian carcinoma cells to the peritoneal mesothelium involves the interaction between CD44S on ovarian carcinoma cells and hyaluronic acid on mesothelial surfaces. We, therefore, analyzed a series of ovarian carcinomas for the expression of CD44S by immunohistochemistry to see whether expression of this receptor by tumor cells correlated with clinicopathological factors and measures of patient outcome. Fifty-six fixed, paraffin-embedded primary epithelial ovarian tumors were immunostained with antibody to CD44S. Membrane staining was considered positive, and results were correlated with stage, grade, age, histology, and survival. Twenty-two (39%) tumors were positive for CD44S. There was no correlation between CD44 expression and histological type, grade, age, or stage. However, CD44 expression was significantly associated with survival in both univariate (P = 0.003) and multivariate (P = 0.006) analyses. These results support a role for CD44S expression in the spread of ovarian epithelial cancer and suggest that expression of this molecule is a significant independent predictor of survival in women with this disease
1512
Isolation and characterization of dermal lymphatic and blood endothelial cells reveal stable and functionally specialized cell lineages.
Kriehuber E,Breiteneder-Geleff S,Groeger M,Soleiman A,Schoppmann SF,Stingl G,Kerjaschki D,Maurer D.
J Exp Med 2001;194:797-808.
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Abstract
A plexus of lymphatic vessels guides interstitial fluid, passenger leukocytes, and tumor cells toward regional lymph nodes. Microvascular endothelial cells (ECs) of lymph channels (LECs) are difficult to distinguish from those of blood vessels (BECs) because both express a similar set of markers, such as CD31, CD34, podocalyxin, von Willebrand factor (vWF), etc. Analysis of the specific properties of LECs was hampered so far by lack of tools to isolate LECs. Recently, the 38-kD mucoprotein podoplanin was found to be expressed by microvascular LECs but not BECs in vivo. Here we isolated for the first time podoplanin(+) LECs and podoplanin(-) BECs from dermal cell suspensions by multicolor flow cytometry. Both EC types were propagated and stably expressed VE-cadherin, CD31, and vWF. Molecules selectively displayed by LECs in vivo, i.e., podoplanin, the hyaluronate receptor LYVE-1, and the vascular endothelial cell growth factor (VEGF)-C receptor, fms-like tyrosine kinase 4 (Flt-4)/VEGFR-3, were strongly expressed by expanded LECs, but not BECs. Conversely, BECs but not LECs expressed VEGF-C. LECs as well as BECs formed junctional contacts with similar molecular composition and ultrastructural features. Nevertheless, the two EC types assembled in vitro in vascular tubes in a strictly homotypic fashion. This EC specialization extends to the secretion of biologically relevant chemotactic factors: LECs, but not BECs, constitutively secrete the CC chemokine receptor (CCR)7 ligand secondary lymphoid tissue chemokine (SLC)/CCL21 at their basal side, while both subsets, upon activation, release macrophage inflammatory protein (MIP)-3alpha/CCL20 apically. These results demonstrate that LECs and BECs constitute stable and specialized EC lineages equipped with the potential to navigate leukocytes and, perhaps also, tumor cells into and out of the tissues.
1294
Isolation and Characterization of Dermal Lymphatic and Blood Endothelial Cells Reveal Stable and Functionally Specialized Cell Lineages
Kriehuber,Ernst; Breiteneder-Geleff,Silvana; Groeger,Marion; Soleiman,Afschin; Schoppmann,Sebastian F.; Stingl,Georg; Kerjaschki,Dontscho; Maurer,Dieter
Journal of Experimental Medicine 2001;194:797-808.
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Abstract
A plexus of lymphatic vessels guides interstitial fluid, passenger leukocytes, and tumor cells toward regional lymph nodes. Microvascular endothelial cells (ECs) of lymph channels (LECs) are difficult to distinguish from those of blood vessels (BECs) because both express a similar set of markers, such as CD31, CD34, podocalyxin, von Willebrand factor (vWF), etc. Analysis of the specific properties of LECs was hampered so far by lack of tools to isolate LECs. Recently, the 38-kD mucoprotein podoplanin was found to be expressed by microvascular LECs but not BECs in vivo. Here we isolated for the first time podoplanin+ LECs and podoplanin- BECs from dermal cell suspensions by multicolor flow cytometry. Both EC types were propagated and stably expressed VE-cadherin, CD31, and vWF. Molecules selectively displayed by LECs in vivo, i.e., podoplanin, the hyaluronate receptor LYVE-1, and the vascular endothelial cell growth factor (VEGF)-C receptor, fms-like tyrosine kinase 4 (Flt-4)/VEGFR-3, were strongly expressed by expanded LECs, but not BECs. Conversely, BECs but not LECs expressed VEGF-C. LECs as well as BECs formed junctional contacts with similar molecular composition and ultrastructural features. Nevertheless, the two EC types assembled in vitro in vascular tubes in a strictly homotypic fashion. This EC specialization extends to the secretion of biologically relevant chemotactic factors: LECs, but not BECs, constitutively secrete the CC chemokine receptor (CCR)7 ligand secondary lymphoid tissue chemokine (SLC)/CCL21 at their basal side, while both subsets, upon activation, release macrophage inflammatory protein (MIP)-3{alpha}/CCL20 apically. These results demonstrate that LECs and BECs constitute stable and specialized EC lineages equipped with the potential to navigate leukocytes and, perhaps also, tumor cells into and out of the tissues
1522
CD44 is a macrophage binding site for Mycobacterium tuberculosis that mediates macrophage recruitment and protective immunity against tuberculosis
Leemans,Jaklien C.; Florquin,Sandrine; Heikens,Mirjam; Pals,Steven T.; Neut,Ronald van der; van der Poll,Tom
Journal of Clinical Investigation 2003;111:681-689.
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Abstract
Cell migration and phagocytosis are both important for controlling Mycobacterium tuberculosis infection and are critically dependent on the reorganization of the cytoskeleton. Since CD44 is an adhesion molecule involved in inflammatory responses and is connected to the actin cytoskeleton, we investigated the role of CD44 in both these processes. Macrophage (M{phi}) recruitment into M. tuberculosis-infected lungs and delayed-type hypersensitivity sites was impaired in CD44-deficient (CD44-/-) mice. In addition, the number of T lymphocytes and the concentration of the protective key cytokine IFN-{gamma} were reduced in the lungs of infected CD44-/- mice. The production of IFN-{gamma} by splenocytes of CD44-/- mice was profoundly increased upon antigen-specific stimulation. Flow cytometry analysis revealed that soluble CD44 can directly bind to virulent M. tuberculosis. Mycobacteria also interacted with M{phi}-associated CD44, as reflected by reduced binding and internalization of bacilli by CD44-/- M{phi}s. This suggests that CD44 is a receptor on M{phi}s for binding of M. tuberculosis. CD44-/- mice displayed a decreased survival and an enhanced mycobacterial outgrowth in lungs and liver during pulmonary tuberculosis. In summary, we have identified CD44 as a new M{phi} binding site for M. tuberculosis that mediates mycobacterial phagocytosis, M{phi} recruitment, and protective immunity against pulmonary tuberculosis
71
An Immunohistochemical Analysis of Canine Haemangioma and Haemangiosarcoma
Sabattini,S.; Bettini,G.
Journal of Comparative Pathology 2009;140:158-168.
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Abstract
The aim of the present study was to investigate immunohistochemically aspects of the biology of canine endothelial neoplasia. Forty samples of canine cutaneous and visceral haemangiosarcoma (HSA), 29 samples of cutaneous and visceral haemangioma (HA) and 10 control samples of granulation tissue (GT) were labelled with antisera specific for vimentin, smooth muscle actin, von Willebrand factor (vWF), CD117 (KIT), vascular endothelial growth factor receptor-3 (VEGFR-3), vascular endothelial growth factor-C (VEGFC) and CD44. Further antisera were employed to determine the level of cellular proliferation (MIB-1 index) and toluidine blue staining was used to detect populations of tumour-infiltrating mast cells (MCs). There was greater expression of CD117, VEGFR-3 and CD44 in HSA than in HA, suggesting that these proteins might be suitable targets for the future development of novel therapeutic approaches to canine HSA. Marked infiltration of MC was detected in HA, suggesting a possible role for these cells in the pathogenesis of benign vascular neoplasia in the dog.
2692
Evaluation of Soluble CD44v6 as a Potential Serum Marker for Head and Neck Squamous Cell Carcinoma
Van Hal,Nicole L.W.; van Dongen,Guus A.M.S.; Ten Brink,Corlinda B.M.; Heider,Karl Heinz; Rech-Weichselbraun,Irene; Snow,Gordon B.; Brakenhoff,Ruud H.
Clinical Cancer Research 1999;5:3534-3541.
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Abstract
In recent years, the measurement of soluble CD44 levels in the circulation of patients with malignant diseases has been introduced as a new and simple diagnostic tool for the detection of human cancer. The high CD44v6 expression in head and neck squamous cell carcinoma (HNSCC) would enable the use of soluble CD44v6 proteins present in the circulation of HNSCC patients as a marker of disease. In the present study, we determined CD44v6 plasma levels using a domain-specific ELISA in healthy volunteers, non-cancer patients, and HNSCC patients before and after surgical removal of the tumor. A difference between the CD44v6 plasma levels of HNSCC patients and controls could not be observed. Moreover, surgical removal of the tumor did not result in a reduction of the CD44v6 plasma level in the HNSCC patients. In addition, the spectrum of soluble v6-containing CD44 proteins present in the plasma of HNSCC patients and controls was determined by immunoprecipitation experiments, but again, tumor-related isoforms could not be distinguished in patient samples. Additional experiments to unravel the biological source of these circulating proteins indicated surprisingly that the v6-containing proteins present in the circulation of healthy individuals are only released in part, if at all, by activated lymphocytes or other nucleated blood cells. Most circulating CD44v6 proteins seem to be derived from the normal epithelial cell compartments, including breast cells, colon cells, and squamous cells. Taken together, these data do not support the use of soluble CD44v6 as a tumor marker in HNSCC or any other tumor type that has developed from tissues producing soluble isoforms
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