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At least 415 records · Page 23Linked to original sources
PubMed2005

Endothelial adhesion of synchronized gastric tumor cells changes during cell cycle transit and correlates with the expression level of CD44 splice variants.

AIM: To study adhesion capacity and CD44 expression of human gastric adenocarcinoma MKN45 cells at different stages of a first cell cycle. METHODS: MKN45 cells were synchronized by aphidicolin and assayed for adhesion to an endothelial cell (HUVEC) monolayer. Surface expression of CD44 and CD44 splice variants on MKN45 cells was evaluated by flow cytometry. Functional relevance of CD44 adhesion receptors was investigated by blocking studies using anti CD44 monoclonal antibodies or by hyaluronan digestion. RESULTS: Adhesion of MKN45 to HUVEC was increased during G2/M transit, after which adhesion returned to baseline levels with cell cycle completion. In parallel, CD44 splice variants CD44v4, CD44v5, and CD44v7 were all up-regulated on MKN45 during cell cycle progression with a maximum effect in G2/M. The function of CD44 surface receptors was assessed with specific receptor blocking monoclonal antibodies or removal of hyaluronan by digestion with hyaluronidase. Both strategies inhibited tumor cell adhesion to HUVEC by nearly 50%, which indicates that MKN45-HUVEC-interaction is CD44 dependent. CONCLUSION: CD44 expression level is linked to the cell cycle in gastrointestinal tumor cells, which in turn leads to cell cycle dependent alterations of their adhesion behaviour to endothelium.

Alternative Splicing↗
PubMed2004

Expression of L-selectin, but not CD44, is required for early neutrophil extravasation in antigen-induced arthritis.

L (leukocyte)-selectin (CD62L) and CD44 are major adhesion receptors that support the rolling of leukocytes on endothelium, the first step of leukocyte entry into inflamed tissue. The specific contribution of L-selectin or CD44 to the regulation of cell traffic to joints in arthritis has not been investigated. We used CD44-deficient, L-selectin-deficient, and CD44/L-selectin double knockout mice to determine the requirement for these receptors for inflammatory cell recruitment during Ag-induced arthritis. Intraperitoneal immunization resulted in similar activation status and Ag-specific responses in wild-type and gene-targeted mice. However, extravasation of neutrophil granulocytes, but not the emigration of T cells, into the knee joints after intra-articular Ag injection was significantly delayed in L-selectin-deficient and double knockout mice. Intravital videomicroscopy on the synovial microcirculation revealed enhanced leukocyte rolling and diminished adherence in mice lacking either CD44 or L-selectin, but CD44 deficiency had no significant effect on the recruitment of L-selectin-null cells. Compared with wild-type leukocytes, expression of L-selectin was down-regulated in CD44-deficient cells in the spleen, peripheral blood, and inflamed joints, suggesting that reduced expression of L-selectin, rather than the lack of CD44, could be responsible for the delayed influx of granulocytes into the joints of CD44-deficient mice. In conclusion, there is a greater requirement for L-selectin than for CD44 for neutrophil extravasation during the early phase of Ag-induced arthritis.

Animals↗
PubMed2000

Cd44: a marker of squamous differentiation in adenosquamous neoplasms.

OBJECTIVE: To test the hypothesis that CD44 standard (CD44[s]) and its other variants, CD44v6 and CD44v7-8, might be useful markers of squamous differentiation in epithelial tumors. DESIGN: We studied expression of CD44(s), CD44v6, and CD44v7-8 using immunohistochemistry in human tumors that had squamous differentiation, glandular differentiation, or both arising in the colon, stomach, esophagus, lung, pancreas, gallbladder, or uterus/cervix, as well as in adjacent nonneoplastic tissues. Formalin-fixed, paraffin-embedded archival tissue specimens of 33 adenosquamous tumors were used. All were stained with monoclonal antibodies against a conserved portion of CD44(s) and its variants, CD44v6 and CD44v7-8, using the avidin-biotin peroxidase method. RESULTS: CD44(s) and its variants consistently and strongly stained areas of tumors with well-developed squamous differentiation. These markers also consistently and strongly stained normal squamous mucosa. Reactivity for CD44 and its variants was lacking in normal glandular type epithelium and in adenocarcinomas composed entirely of well-differentiated mucin-producing glands. Areas of well-differentiated carcinoma, both squamous and adenocarcinoma, were consistent with respect to both extent and intensity of staining. Staining in lymph nodes was similar to that in the primary tumors, with well-differentiated squamous foci being consistently positive, well-differentiated mucin-producing adenocarcinoma foci consistently negative, and poorly differentiated foci showing variable staining. Although staining was less intense with the variants, it followed the same staining pattern as found for CD44(s). No differences in the extent or intensity of staining were identified in the metastatic versus primary tumor foci, nor was any difference identified between superficial and deeply invasive areas of primary tumors. CONCLUSIONS: Our study shows that CD44(s) and its variants are good markers of squamous epithelial differentiation in several types of normal epithelium and tumors, and that these markers can identify areas of well- to moderately differentiated elements in adenosquamous neoplasms. However, poorly differentiated tumors show an inconsistent staining pattern with CD44, such that it cannot be used as a reliable and practical marker of squamous differentiation in poorly differentiated neoplasms.

Adenocarcinoma↗
PubMed1999

CD44 stimulation induces integrin-mediated adhesion of colon cancer cell lines to endothelial cells by up-regulation of integrins and c-Met and activation of integrins.

For cancer metastasis, tumor cells present in the circulation must first adhere to the endothelium. Integrins lymphocyte function-associated antigen (LFA) 1 and very late antigen 4 play a central role in leukocyte adhesion to the endothelium and subsequent migration into tissues. The majority of tumor cells derived from solid cancers including colorectal cancer do not express suitable adhesion receptors, LFA-1 and very late antigen 4. We investigated the mechanisms of adhesion and transendothelial migration of cancer cells using colorectal carcinoma cell lines. Our results showed the following novel features of CD44 on the cells: (a) colon cancer cells express high levels of CD44; (b) stimulation of cancer cells by CD44 cross-linking or fragmented hyaluronan markedly induces the expression of LFA-1s, some of which reveal an activation epitope on the cells; (c) CD44 cross-linking induces F-actin polymerization in the cell cortex; (d) fragmented hyaluronan induces up-regulation of the activation epitope of LFA-1, which is mediated through protein kinase C; (e) stimulation of CD44 augments the LFA-1-mediated adhesion of cancer cells to endothelial cells and intercellular adhesion molecule 1-transfected cells and facilitates transendothelial migration; (f) stimulation of CD44 also induces expression of the hepatocyte growth factor (HGF) receptor c-Met on cancer cells; and (g) HGF further amplifies the LFA-1-mediated adhesion of cells prestimulated by CD44-derived signaling. Our results indicated that stimulation by CD44 induces "outside-in signaling," which consists of a direct pathway via CD44 and an alternate pathway through the induction of c-Met expression via HGF. Such stimuli augment the expression and trigger the function of integrins via "inside-out signaling" in colon cancer cells, which leads to amplification of integrin-mediated adhesion to the vessel wall and subsequent transendothelial migration.

Actins↗
PubMed2000

Molecular organization, structural features, and ligand binding characteristics of CD44, a highly variable cell surface glycoprotein with multiple functions.

CD44 is a type I transmembrane protein and member of the cartilage link protein family. It is involved in cell-cell and cell-matrix interactions and signal transduction. Several CD44 ligands have been identified. CD44 is a major cell surface receptor for hyaluronan, a component of the extracellular matrix. It is implicated in diseases such as cancer and inflammation and therefore intensely studied. A characteristic feature of CD44 is the occurrence of many isoforms that are expressed in a cell-specific manner and differentially glycosylated. Although a number of CD44 isoforms have been characterized, the structural diversity of CD44 makes it often challenging to study (isoform-specific) CD44-ligand interactions at the molecular level of detail. The structural organization and ligand binding characteristics of CD44 are focal points of this review. On the basis of recent structural and mutagenesis studies, details of the CD44-hyaluronan interaction are beginning to be understood. Proteins 2000;39:103-111.

Humans↗
PubMed2000

Immunohistochemical study of hyaluronate receptor (CD44) in alcoholic liver disease.

BACKGROUND: It has been suggested that the elevation of serum hyaluronate (HA) levels in liver diseases may be due to increased synthesis of HA by hepatic stellate cells or decreased degradation by sinusoidal endothelial cells. The increase in serum HA levels in patients with cirrhosis is thought to be a response to a reduction in HA receptors (CD44) in hepatic sinusoidal endothelial cells. To learn more about how alcohol affects the number and distribution of HA receptors of hepatic sinusoidal endothelial cells, we immunohistochemically studied CD44 levels in liver biopsy obtained from patients with alcoholic liver disease (ALD patients) and also from patients with nonalcoholic liver disease (non-ALD); ALD patients were evaluated when they were currently drinking and again after they became abstinent. Normal liver tissue obtained from three autopsy cases served as a control. METHODS: Liver biopsy specimens were obtained from 18 ALD patients and 12 non-ALD patients. In ALD patients, liver biopsy was performed twice within 3 days and 4 to 8 weeks after abstinence when serum levels of aspartate aminotransferase and alanine aminotransferase became normal. CD44 in liver specimens was stained with anti-CD44 antibody by streptavidine-biotin-peroxidase complex. The intensity of the staining of CD44 in liver tissue was determined by a computer-assisted imaging analyzer. We also measured serum levels of CD44 in both ALD and non-ALD patients. RESULTS: The intensity and the number of CD44 staining increased in both ALD and non-ALD patients compared with those in normal liver, which was negative. The staining intensity of CD44 in liver specimens obtained from patients with ALD who were active in alcohol consumption were significantly higher when compared with patients with ALD after abstinence. Serum levels of CD44 in patients with liver disease increased compared with those of healthy subjects. CONCLUSIONS: The results suggest that HA receptors may increase to degrade the increased HA in serum and/or liver.

Aged↗
PubMed2001

Zymosan modulates CD44 isoform expression in a murine model of inflammation resembling rheumatoid arthritis synovitis.

OBJECTIVE: To study local inflammation induced by zymosan in the murine air pouch, considered a model of synovial-like tissue inflammation, we investigated the time-course synthesis of CD44 and tumor necrosis factor-alpha (TNF-alpha) mRNA and established a relationship with leukocyte migration into the air pouch and CD44 expression on the leukocyte membrane. METHODS: Leukocytes from the air pouch exudate were collected and counted at 1, 4, 12, 24, 48, and 72 h after zymosan or saline injection. CD44 and TNF-alpha mRNA were studied by RT-PCR. CD44 variable exon analysis was assessed by Southern blot and CD44 membrane expression by flow cytometry. RESULTS: Leukocyte accumulation after zymosan injection was significantly higher than in saline injected controls. CD44 standard and variable isoforms including at least variable exons v6 and v9 were highly expressed in leukocytes from the zymosan air pouch exudate. In contrast, only the CD44 mRNA standard isoform was present in leukocytes from saline air pouch. Maximal TNF-alpha mRNA level was observed at 48 h after zymosan injection, whereas CD44 mRNA was constantly expressed throughout the whole term of the experiment, although variations in leukocyte count and relative formula were observed. CONCLUSION: Expression of CD44 variable isoform in leukocytes was specifically induced by zymosan, since none was detected in saline controls. TNF-alpha mRNA expression and leukocyte count at every time point served as markers for local inflammation. The presence of variable isoforms, including at least exons v6 and v9, consistently expressed throughout the assay suggests that they could play a role in this arthritis-like inflammation induced under zymosan stimulus.

Animals↗
PubMed2001

[CD44 (HCAM) expression in subserous gallbladder carcinoma].

BACKGROUND: HCAM or CD44 is a multifunctional cell adhesion molecule, related to cell-cell, cell-extracellular matrix interactions and involved in tumor invasion. AIM: To study the importance of CD44 expression in subserous gallbladder carcinoma. MATERIAL AND METHODS: One hundred five samples (93 female) of subserous gallbladder carcinoma and 33 non tumoral gallbladder were studied. CD44 was stained using the streptavidine-biotin technique, using human anti CD44 antibodies. Eighty subjects with carcinoma were followed for a period up to 105 months. RESULTS: Mean age of patients was 62.6 years old, all tumors were adenocarcinoma, all were silent and 13% were well differentiated. CD44 was expressed in all controls and in 91%, the expression was normal. In 57% of cancer samples, CD44 expression was abnormal, in 50% it was less expressed and in 24%, it was not expressed. No differences in CD44 expression was observed between mucosa from control samples and mucosa adjacent to the tumor or superficial or deep tumoral areas. Global five years survival was 40%. No significant differences in survival were observed in those tumors with a lower of absent CD44 expression. Six patients with a higher expression died before 18 months of follow up. CONCLUSIONS: Nearly 50% of subserous gallbladder carcinomas show an abnormal CD44 expression.

Adenocarcinoma↗
PubMed2001

[Quantitative studies on expression of peripheral blood CD44 and CD54 in non-small cell lung carcinoma].

OBJECTIVE: To assess the relationship between expression of peripheral blood CD44 and CD54 in lymphocyte with non-small cell lung cancer and clinicopathological features. METHODS: Peripheral blood CD44 contents in 50 patients with lung cancer were detected by flow-cytometry, 30 normal donors and 25 patients with benign lesions served as controls. RESULTS: Peripheral blood CD44 and CD54 in lymphocyte with lung cancer were significantly higher than those in benign lesions and normal controls (P < 0.01). There is no distinct difference between CD44 and CD54 in benign lesions and normal controls (P > 0.05). Lung cancer with lymph node metastasis showed higher expression of CD44 and CD54 than lung cancer without lymph node metastasis (P < 0.01). Distinctly statistic difference was showed between CD44 in stage III, IV and stage I, II (P < 0.01). CD54 content in stage IV was higher than that in stage I, II and III, respectively. Histopathological grade was significantly associated with the expression of CD44 and CD54. Peripheral blood CD44 and CD54 contents were not related with squamous cell carcinoma and adenocarcinoma. CONCLUSION: Detection of CD44 and CD54 levels by flow cytometry might be used as a marker to evaluate prognosis and metastasis in patients with non-small cell lung cancer.

Adult↗
PubMed2001

CD44 expression in colorectal cancer. An immunohistochemical study including correlation with cathepsin D immunoreactivity and some tumour clinicopathological features.

CD44 is a cell adhesion molecule involved in tumour growth and progression. This study was undertaken to evaluate the expression of CD44 standard protein in a series of 54 colorectal adenocarcinomas in correlation with cathepsin D immunoreactivity and some other clinicopathological variables. Formalin-fixed and paraffin-embedded tissues were investigated with anti-CD44 standard protein and anti-cathepsin D antibody. Immunolocalisation of CD44 protein and cathepsin D was performed using LSAB method. 13 (41.9%) out of 31 carcinomas without lymph-node metastases had positive CD44 expression, whereas only 6 (26.1%) out of 23 carcinomas with lymph-node metastases were found positive for CD44 expression. CD44 expression in carcinomas was positively correlated with tumour cells cathepsin D (p<0.01) immunostaining. statistically significant correlation was found between the expression of CD44 standard protein and the tumour site, age and sex of the patients. These results suggest that the standard-type CD44 protein lymph-node metastases, probably with cooperation of cathepsin D.

Adenocarcinoma↗
PubMed2002

Distribution and expression of CD44 isoforms and Ezrin during prostate cancer-endothelium interaction.

CD44 is a multifunctional cell surface adhesion molecule that has been implicated in tumour cell invasion and metastasis. Many cancer cell types as well as their metastases express high levels of CD44. Furthermore, the expression of certain CD44 variants has been linked with metastasis and tumour progression. It is known that ezrin, a member of the ERM family of proteins, can bind to CD44 and thus raises the possibility that it is involved in cell migration and metastasis. Therefore we examined the expression and distribution of CD44, its co-localisation and translocation with ezrin in prostate cancer cell lines as they interact with endothelial cells. Experimental results indicate prostate cancer cells express multiple CD44 isoforms that co-localise with ezrin in DU-145 and PC-3 prostate cancer cells. Treatment with hepatocyte growth factor (HGF/SF) resulted in up-regulation of CD44 and its co-translocation with ezrin during tumour-endothelial cell interactions. In addition, tumour cell adhesion to endothelial cells and their invasiveness was increased after exposure to HGF/SF, and can be blocked by the presence of anti-CD44 antibodies. It is concluded that CD44 and ezrin interact in endothelial cells and that they co-localise in the areas of tumour-endothelial contact. The CD44/ezrin complex plays a pivotal role in the capture and invasion of endothelial cells by prostate cancer cells.

Cytoskeletal Proteins↗
PubMed2003

[The expression of CD44 and it's significance in human laryngeal carcinoma].

OBJECTIVE: To explore the CD44 expression in different laryngeal carcinoma tissues and their clinical significance. METHOD: Using immunohistochemistry methods to study 261 cases of archived paraffin-embedded laryngeal tissue. RESULT: The results turned out to be as follows: 1. A high level of CD44 expression was more frequently found in laryngeal carcinoma than in precarcinoma lesions and normal tissues. 2. CD44 expression correlated well with histological grades, the higher grade the lower the CD44 expression. 3. The third and fourth stages laryngeal carcinoma had stronger CD44 positive than those of the first and second stages. 4. CD44 expression in laryngeal carcinoma with cervical metastasis were higher than those without cervical metastasis. 5. To 3 and 5 years survival, CD44 positive cases had lower chance than CD44 negative cases. CONCLUSION: These results implicates that the occurrence, development and prognosis of laryngeal carcinoma may be closely related to CD44 expression.

Adult↗
PubMed2004

[Relationship between the levels of KAI1/CD82 and CD44 and the clinicopathological features of non-small cell lung cancer].

OBJECTIVE: To observe the relationship between levels of KAI1/CD82 and CD44 in lung carcinomas and their clinicopathological features, in association with the results of metastasis. METHODS: The expressions of KAI1/CD82 and CD44 in 45 patients with lung cancer were detected by flow-cytometry. Tissue samples 3 cm (control group 1) and 5 cm (control group 2) from the cancerous lesions and benign lesions from 30 patients (control group 3) were also studied, and the results were compared. RESULTS: The expression level of KAI1/CD82 protein in lung cancer was lower than that in other three groups (P < 0.01), while the expression level of CD44 was higher than that in other three groups (P < 0.01). The expression level of KAI1/CD82 in control group 1 was also lower than that in control group 2 and benign lesion group (P < 0.05). The expression level of CD44 was higher than that in control group 2 and benign lesion group (P < 0.05). There was no significant difference between the expression level of CD44 and KAI1/CD82 in control group 2 and benign lesion group (P > 0.05). The expression level of KAI1/CD82 and CD44 were closely correlated with clinical staging, pathological differentiation and lymph node metastasis (P < 0.01), but their expressions were not correlated with sex, age, tumor size and pathological type (P > 0.05). Statistic difference was found between KAI1/CD82 and CD44 in primary lesions and metastatic lesions (P < 0.01). There was an inversely correlation between the expression of CD44 and KAI1/CD82 in clinical staging and lymph node metastasis (P < 0.01). CONCLUSION: KAI1/CD82 and CD44 may play an important regulating role in the genesis, development and metastasis of lung cancer, and they may be used as potential markers for tumor metastasis.

Adult↗
PubMed2005

CD44 splicing pattern is associated with disease progression in pulmonary adenocarcinoma.

BACKGROUND AND PURPOSE: Certain alternatively spliced exons of CD44 gene have been associated with specific functions. However, these functions may have come from inclusion of a central array of alternatively spliced exons, rather than a single one. The goals of this study were to analyze all of the variant exons included by alternative splicing, the entire population of CD44 mRNA transcripts, and the prognostic implications of CD44 mRNA and protein isoforms expressed by non-small cell lung cancer (NSCLC). METHODS: Using a polymerase chain reaction protocol with short reaction times, we amplified, sequenced and quantified CD44 mRNA transcripts from 52 samples of NSCLC to determine the splicing patterns of alternatively included exons and the proportion of each CD44 mRNA transcript. The expression of CD44 standard form and variant isoforms CD44v3 and CD44v6 were also analyzed by immunohistochemistry (IHC). RESULTS: Normal lung and NSCLC expressed CD44 mRNA transcripts containing variant exons v10, v8-10, v6-10, v3-10 and v2-10. In squamous cell carcinoma, the expression rates of these mRNA transcripts were equal to or higher than those of the normal lung, and the splicing pattern was not associated with disease progression. In adenocarcinoma, the expression rates of CD44v6-10, v3-10 and v2-10 mRNA were lower than in normal lung. The down-regulation of CD44v6-10, CD44v3-10 mRNA and CD44v6 protein paralleled the progression of adenocarcinoma. Recurrence of adenocarcinoma was associated with negative expression of CD44v6-10 or CD44v3-10 mRNA, and with low-level expression of CD44v6 or CD44v3 by IHC. Negative expression of CD44v6-10 mRNA and reduced expression of CD44 v6 protein were associated with a shorter disease-free and overall survival in the univariate but not the multivariate analysis. CONCLUSION: Our data suggest that CD44 splicing pattern is associated with disease progression in adenocarcinoma.

Adenocarcinoma↗
PubMed1995

CD44 expression in rejecting rat small bowel allografts.

CD44 is a widely expressed cell surface protein that recognizes multiple ligands and is involved in extra- and intercellular adhesion. The precise role of CD44 in immune interactions is currently unknown, but it is believed to be a homing receptor involved in lymphocyte trafficking and inflammatory responses. This study investigated CD44 expression in intestinal tissue after heterotopic rat small bowel transplantation and assessed the effect of transplantation on intestinal epithelial cell proliferation using an antibody to the nuclear activation Ag Ki67. Lamina propria and intestinal epithelial cell expression of CD44 was graded blindly by five observers, and villus epithelial cells were noted as being positive or negative for Ki67 staining. CD44 expression was high in the lamina propria of both allografted and isografted animals; however, there was no significant difference between the two groups. In contrast, the expression of CD44 on the villus epithelium was greater in allografted animals and progressed toward the villus tips as rejection developed, declining thereafter because of loss of villus integrity. Ki67 positivity was also greater in allografted animals but did not progress toward the villus tip. This is the first reported observation of CD44 expression on intestinal epithelium that is not restricted to the crypts. The findings indicate the involvement of CD44 in the rejection process and demonstrate changes in the proliferative profile of rejecting small intestinal epithelium. Further studies into adhesion molecules, such as CD44, may help to improve understanding of graft failure and promote the development of new therapeutic approaches for controlling and preventing graft rejection.

Animals↗
PubMed1994

Inducible binding of human lymphocytes to hyaluronate via CD44 does not require cytoskeleton association but does require new protein synthesis.

We have examined molecular mechanisms of the PMA-inducible HA binding ability of human lymphocytes. Newly established OS/6 and OS/37, specific for human CD44, specifically inhibited PMA-induced HA binding of several human cell lines, suggesting that both mAb detect HA binding epitope(s) on CD44. Sequential staining revealed that these mAb cross-blocked each other's binding to Molt-4, T lymphoblast lines, and that neither of them interfered with staining of Molt-4 by other anti-CD44 mAb which induced significant homotypic cell aggregation. Biochemical and PCR analyses did not provide any evidence that PMA stimulation induced dramatic changes in molecular weight or molecular isoforms of CD44. Interestingly, HA binding was not affected and rather slightly increased by cytochalasin B which disrupts F-actin microfilament integrity. This suggests that the ability of CD44 to bind to HA does not correlate with the association of CD44 with the cytoskeleton. On the other hand, protein synthesis inhibitors, cycloheximide and anisomycin clearly inhibited the induction of HA binding of PMA-activated Molt-4 without affecting the expression of CD44 at the same time after stimulation. The same treatment had no effect on PMA-induced FN binding of the cells, which was mediated by VLA integrins. These results suggest that the adhesion functions of CD44 and integrins are differently regulated despite the fact that both are induced by PMA stimulation, and that new protein synthesis is essential for the PMA-induced HA binding by CD44.

Anisomycin↗
PubMed1994

CD44 mediates human glioma cell adhesion and invasion in vitro.

Human gliomas are characterized by their invasion of normal brain structures irrespective of their grade of malignancy. Factors involved in the control of this invasive behavior are poorly documented. Human gliomas have also been found to express CD44 adhesion molecules. Expression of splice variants of CD44 has been correlated to metastasis in nonglial solid tumors. In this study, 8-microns porosity polycarbonate filters incorporated in modified Boyden chambers and coated with the extracellular matrix composite Matrigel were used to investigate the role of CD44 in invasion of eight human glioma cell lines in vitro. Invasion of Matrigel was found to be inhibited to different extents by a CD44 monoclonal antibody. Moreover, this invasion was highly inhibited in two cell lines and completely arrested in five other glioma cell lines by a CD44-specific antisense oligonucleotide which inhibited CD44 expression. In addition, adhesion of glioma cells to fibronectin, laminin, vitronectin, and collagen I was inhibited by the CD44 monoclonal antibody. These results strongly suggest that CD44 is involved in human glioma cell invasion in vitro, probably through its role in cell interactions with extracellular matrix proteins. Interference with glioma invasion, by targeting CD44 expression, may be envisaged in animal models.

Base Sequence↗
PubMed1994

CD44 triggering enhances human NK cell cytotoxic functions.

CD44, a major hyaluronate receptor, is involved in a variety of lymphocyte functions including lympho-hemopoiesis, adhesion to high endothelial venules or the extracellular matrix, and T cell activation. Here we investigated the ability of CD44 to affect the cytotoxic functions of human NK cells. Ligation of CD44 by selected mAb (J173 and F10442) resulted in a rapid, dose-response-dependent enhancement of NK cytotoxic activity against a panel of tumor target cells that varied in their sensitivity to NK killing. Neither enhanced killing against NK-resistant target cells nor CD44 mAb-mediated redirected lysis was not observed. CD44 cross-linking also was found to up-regulate CD16-mediated lysis. In an attempt to investigate the early biochemical events that occur after CD44 ligation, we found that optimal cross-linking conditions induce a rapid increase of intracellular free calcium levels, which is abrogated by extracellular Ca2+ chelation. Moreover, enhanced and more sustained Ca2+ rise resulted from CD16 and CD44 coengagement. In contrast, no inositol 1,4,5-trisphosphate generation was found after optimal CD44 cross-linking. These results suggest that although CD44 is not capable of delivering a lytic signal in human NK cells, it coactivates spontaneous or CD16-mediated NK cytotoxicity. The variation in intracellular free calcium may be one of the signals that account for the costimulation of the lytic activity.

Antibodies, Monoclonal↗