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CD44 Expression (cd44 + expression)
Selected AbstractsHyaluronan and its receptors in mucoepidermoid carcinomaHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 2 2006Richard O. Wein MD Abstract Background. Hyaluronan (HA) is a prominent extracellular matrix component undergoing continuous production and degradation. Increased HA levels have been described in a variety of tumors. The objective of this study was to examine the staining patterns of HA and two of its associated receptors (CD44 and HARE) in relation to the metastatic potential of mucoepidermoid carcinoma (MC). Immunohistochemical staining of preserved surgical specimens was used. Methods. Tissues from 12 patients with a histologic diagnosis of salivary MC (10 parotid, one submandibular gland, one minor salivary gland) were studied. Half (six of 12) of the patients had regional metastases. Tumor, normal salivary tissue, and regional lymph nodes were stained for HA, CD44, and HARE expression. Specimens were graded for staining intensity and a percent of the specimen stained. Results. Normal salivary tissue did not demonstrate epithelial cell surface HA expression, whereas HA was expressed on tumor cells and in regional lymph nodes containing metastases. These differences were both significant using Student's t test (p < .00002, and p < .0022, respectively). Tumors with positive nodes tended to have greater cell surface HA. Decreased expression or downregulation of HARE was also noted in involved lymph nodes. No differences in CD44 expression were seen between primary specimens and lymph nodes. The observed staining patterns for CD44 and HARE were not reflective of the metastatic potential of the primary MC. Conclusions. Increased HA expression was seen on mucoepidermoid carcinoma cells compared with adjacent normal salivary gland epithelium. This observation may assist in explaining the development of regional metastasis in these tumors. We did not identify specific HA, CD44, or HARE staining patterns in primary lesions that were predictive of regional metastases. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX,XXX, 2005 [source] CD44 isoform expression in synovial sarcoma correlates with epitheliogenesis but not prognosisHISTOPATHOLOGY, Issue 2 2000R J Sneath Aims : We immunohistochemically determined the expression of CD44 standard and splice variant isoforms in a series of synovial sarcomas and sought correlations with histological subtype and clinical parameters including outcome. Methods, and results: From 39 patients, a total of 56 formalin-fixed and paraffin-embedded tumour samples (including initial, recurrent and metastatic tumours) were used to immunohistochemically evaluate the expression of epitopes encoded by CD44s and the CD44 splice variants CD44v3,v10. Significance of proposed prognostic indicators was evaluated in relation to the survival, time to local recurrence and time to metastases using log-rank analysis. Sixty-four percent of synovial sarcomas expressed CD44s and 46% expressed CD44v3,v10 (var). Synovial sarcomas with epithelial or epithelioid areas preferentially expressed CD44s in these areas when compared with the spindle cell element. There were no correlations with clinical parameters or outcome. Conclusions: The expression of CD44 was not found to correlate with survival, local recurrence or metastatic ability. In synovial sarcoma, CD44 and variant isoform expression appears to be associated with the degree of epithelial differentiation. CD44 expression in synovial sarcoma shows interesting similarities to CD44 expression in embryological epitheliogenesis. [source] Direct and indirect manipulation of the MEK-ERK pathway regulates the formation of a pericellular HA-dependent matrix by chick articular surface cells without modifying CD44 expresssionINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2004Edward R. Bastow Introduction Recent evidence suggests that hyaluronan (HA) facilitates the mechano-dependent joint cavity-forming process through the elaboration and retention of a HA-rich pericellular matrix in the developing joint interzone (IZ). The presumptive joint IZ phenotype shows a capacity to bind and synthesize HA and also exhibits elevated activated ERK, prior to synovial joint cavity formation (Lamb et al. 2001; Edwards et al. 1994; Dowthwaite et al. 1998). We have found that immobilization, which induces embryonic joint fusion with loss of the joint IZ phenotype, also reduces ERK activity levels in the IZ. As the signalling events regulating the synthesis and binding of HA have yet to be determined, we hypothesize that ERK activation plays a pivotal role in determining the presumptive joint IZ phenotype through HA synthetic and binding capacity. Materials and methods Chick articular surface (AS) cells were harvested from proximal tibiotarsal joints of embryos by collagenase digestion. Pericellular coat formation was assessed using the erythrocyte exclusion assay and cell-coat area ratios determined. ERK activity was modulated by transient transfection of GFP constructs of constitutively active (CA-) or dominant negative (DN-) forms of MEK, the direct upstream regulator of ERK or by treatment with the MEK inhibitor PD98059 (50 µm). ERK activation was monitored by immunochemistry. CD44 expression and ERK activation in PD98059-treated cells were monitored by immunoblotting and medium HA concentrations by ELISA. Results AS cells form large pericellular coats that are lost following hyaluronidase treatment and thus dependent upon HA for their construction. Treatment with PD98059 significantly reduced pericellular coat formation after 6 h. In parallel, we confirmed that PD98059 diminished active ERK expression without modifying overall levels of ERK, suggesting that the elaboration of large HA-pericellular coats is dependent upon MEK's activation of ERK. Western blot analysis of PD98059-treated cells showed that loss of pericellular coats was not, however, associated with any decreased levels of the cell surface HA receptor CD44. Although treatment with PD98059 did not change medium HA concentration after short times of exposure, at times (up to 6 h) during which coat loss was evident, prolonged treatment over 24 h significantly decreased medium HA concentration. Consistent with a role for ERK in pericellular coat formation, transfection with DN-MEK diminished, while CA-MEK increased, both active ERK expression and coat formation efficiency. We also found that, commensurate with this modification in coat forming efficiency, cells expressing DN-MEK exhibited a significant reduction in labelling of free HA on the cell surface. Discussion These studies extend our recent work to indicate that: (i) direct modulation of ERK activation by transfection with its endogenous upstream regulator modifies cell surface-associated HA (ii) PD98059-induced blockade of ERK activation restricts medium HA release and (iii) ERK-mediated changes in pericellular coat elaboration are independent of changes in cellular CD44 expression. These findings suggest an intimate relationship between ERK activation and the formation/retention of HA-rich pericellular matrices in vitro and highlight the role for ERK activation in regulating joint line-related differentiation. [source] Systemic and local effects of long-term exposure to alkaline drinking water in ratsINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2001Marina E.T. Merne Alkaline conditions in the oral cavity may be caused by a variety of stimuli, including tobacco products, antacids, alkaline drinking water or bicarbonate toothpaste. The effects of alkaline pH on oral mucosa have not been systematically studied. To assess the systemic (organ) and local (oral mucosal) effects of alkalinity, drinking water supplemented with Ca(OH)2 or NaOH, with pH 11.2 or 12 was administered to rats (n = 36) for 52 weeks. Tissues were subjected to histopathological examination; oral mucosal biopsy samples were also subjected to immunohistochemical (IHC) analyses for pankeratin, CK19, CK5, CK4, PCNA, ICAM-1, CD44, CD68, S-100, HSP 60, HSP70, and HSP90. At completion of the study, animals in the study groups had lower body weights (up to 29% less) than controls despite equal food and water intake, suggesting a systemic response to the alkaline treatment. The lowest body weight was found in rats exposed to water with the highest pH value and starting the experiment when young (6 weeks). No histological changes attributable to alkaline exposure occurred in the oral mucosa or other tissues studied. Alkaline exposure did not affect cell proliferation in the oral epithelium, as shown by the equal expression of PCNA in groups. The up-regulation of HSP70 protein expression in the oral mucosa of rats exposed to alkaline water, especially Ca(OH)2 treated rats, may indicate a protective response. Intercellular adhesion molecule-1 (ICAM-1) positivity was lost in 6/12 rats treated with Ca(OH)2 with pH 11.2, and loss of CD44 expression was seen in 3/6 rats in both study groups exposed to alkaline water with pH 12. The results suggest that the oral mucosa in rats is resistant to the effects of highly alkaline drinking water. However, high alkalinity may have some unknown systemic effects leading to growth retardation, the cause of which remains to be determined. [source] Involvement of vascular endothelial growth factor, CD44 and CD133 in periodontal disease and diabetes: an immunohistochemical studyJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 1 2009Guendalina Lucarini Abstract Aim: The aim of this study was to investigate the relationship between expression of angiogenic and regeneration markers and periodontal disease in subjects with/without diabetes mellitus. Material and Methods: Immunohistochemical detection of vascular endothelial growth factor (VEGF), CD44 and CD133 was performed in 16 samples each of (1) healthy gingiva from non-diabetic subjects (controls), (2) gingiva from non-diabetic subjects with periodontitis, (3) gingiva from subjects with type 1 diabetes and periodontitis, (4) gingiva from subjects with type 2 diabetes and periodontitis. Results: Diseased gingivae from patients with diabetes and periodontitis had greater clinical measures of periodontal disease than those with periodontitis only. VEGF expression was significantly enhanced in epithelial and endothelial cells from patients with periodontitis compared with controls (p<0.05). Epithelial CD44 expression was strong in all groups, while CD44 was significantly enhanced (p<0.05) in connective tissue cells from both diabetic groups. Epithelial and endothelial CD133 expression was comparable in all patients except those with type 2 diabetes and periodontitis, where it was not detected. Stromal CD133 expression was significantly lower in patients with type 2 diabetes and periodontitis and was increased in periodontitis patients (p<0.05). Conclusions: The involvement and high expression of VEGF, CD44 and CD133 in periodontal disease may predict a greater regeneration capacity of gingival tissue. [source] Expression of CD44s and CD44v6 in transitional cell carcinomas of the urinary bladder: comparison with tumour grade, proliferative activity and p53 immunoreactivity of tumour cells,APMIS, Issue 11 2007JITKA KUNCOVÁ Alterations of CD44 glycoproteins have been shown to play an important role in progression of various malignancies, including urothelial cancer. We investigated expression patterns of CD44s and CD44v6 in transitional cell carcinoma (TCC) of the urinary bladder in relation to tumour grade, proliferative activity, and immunoreactivity for p53. The selected markers were detected immunohistochemically in 122 samples of TCC. We found a close relationship between CD44s and CD44v6 expression and tumour grade. The extension of positive staining for CD44s and CD44v6 towards the luminal surface was a predominant feature of differentiated carcinomas (grades 1 and 2), suggesting deranged maturation of cancer cells related to their neoplastic transformation. Heterogeneous expression of CD44s and CD44v6 predominated in poorly differentiated tumours (G3,4). However, areas of squamous differentiation within the high-grade tumours displayed strong immunoreactivity for both CD44s and CD44v6. The proliferative activity and p53 overexpression increased with the dedifferentiation of the tumour. The results of this study are discussed in relation to the significance of CD44 expression in TCC and to the explanation for controversial results reported in previous studies on the relationship between CD44 expression and the biological behaviour of urothelial cells. [source] A role for ,/, T cells in a mouse model of fracture healingARTHRITIS & RHEUMATISM, Issue 6 2009Nona T. Colburn Objective Fractures can initiate an immune response that disturbs osteoblastic and osteoclastic cellular homeostasis through cytokine production and release. The aim of our study was to investigate ,/, T cells, innate lymphocytes known to be involved in tissue repair, as potential cellular components of the osteoimmune system's response to an in vivo model of bone injury. The absence of such cells or their effector cytokines influences the fate of other responder cells in proliferation, differentiation, matrix production, and ultimate callus formation. Methods Tibia fractures were created in 60 ,/, T cell,deficient mice (also called , T cell receptor [TCR],knockout mice) and 60 control C57BL/6 mice. Analysis included radiographs, basic histology, mechanical testing, flow cytometry, and immunohistochemical localization of ,/, TCR,positive subsets from control animals and of CD44 expression from both groups, as well as enzyme-linked immunosorbent assay for the effector cytokines interleukin-2 (IL-2), interferon-, (IFN,), and IL-6. Results Animals deficient in ,/, T cells demonstrated more mature histologic elements and quantitative increases in the expression of major bone (bone sialoprotein) and cartilage (type II collagen) matrix proteins and in the expression of bone morphogenetic protein 2 at a critical reparative phase. Moreover, only ,/, T cell,deficient animals had a decrease in the osteoprogenitor antiproliferative cytokines IL-6 and IFN, at the reparative phase. The result was improved stability at the repair site and an overall superior biomechanical strength in ,/, T cell,deficient mice compared with controls. Conclusion The evidence for a role of ,/, T cells in the context of skeletal injury demonstrates the importance of the immune system's effect on bone biology, which is relevant to the field of osteoimmunology, and offers a potential molecular platform from which to develop essential therapeutic strategies. [source] Effects of a 50 Hz sinusoidal magnetic field on cell adhesion molecule expression in two human osteosarcoma cell lines (MG-63 and Saos-2)BIOELECTROMAGNETICS, Issue 5 2003Maria Teresa Santini Abstract The possibility that a sinusoidal 50 Hz magnetic field with a magnetic flux density of 0.5 mT can induce variations in the expression of cell adhesion molecules (CAMs) in two human osteosarcoma cell lines (MG-63 and Saos-2) was investigated. In particular, the expression of two important integrins, VLA-2, the receptor for collagen, and VLA-5, the receptor for fibronectin, as well as CD44, were examined in both cell lines after these had been exposed for 7 and 14 days to a 50 Hz, 0.5 mT field. Cell surface morphology (scanning electron microscopy), cell growth characteristics (growth curves and cell cycle phase distribution), and cell death (necrosis and apoptosis) were also examined. The results demonstrate that no variations in surface morphology and cell death occurred between control and exposed cells in both MG-63 and Saos-2 cells, while significant changes were noted in cell growth and fibronectin and CD44 expression in MG-63 cells. The results are discussed in view of the important role that CAMs play in controlling various cancer cell functions, particularly proliferation and metastasis. Bioelectromagnetics 24:327-338, 2003. © 2003 Wiley-Liss, Inc. [source] | ||||||||||