Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Solitary stroma-invading tumor cells expressing the ATP-binding cassette transporter P-glycoprotein have been reported to be associated with a significantly higher incidence of vessel invasion and lymph node metastases. In contrast to P-gp-mediated multidrug resistance (MDR) which has become well characterized over the last decade, little is known about further morphological and functional alterations in drug-resistant tumor cells. Binding of malignant cells to components of the extracellular matrix mediated by beta 1 integrins has been suggested to play a substantial role in the metastatic cascade. We studied alterations of beta 1 integrin expression and in vitro adhesiveness to extracellular matrix proteins of the human renal carcinoma line Caki-1 in comparison to the vinblastine resistant sublines Caki-1/V1 and Caki-1/V10 (cultured in the presence of 1 ng/ml and 10 ng/ml vinblastine, respectively). Both VLA-1 and VLA-2 receptors were acquired by the Caki-1/V10 subline, whereas untreated and Caki-1/VI cells lacked surface expression of these antigens. VLA-6 was found to be decreased in the vinblastine-resistant sublines. Attachment of drug-resistant Caki-1/V1 and Caki-1/V10 cells to collagen type I was significantly increased when compared to parental cells (p < or = 0.005). Significant differences in the attachment to type IV collagen were observed between Caki-1/V10 and untreated cells (p < or = 0.045). Both Caki-1/V1 and Caki-1/ V10 cells exhibited increased adhesion to fibronectin when compared to cells of the untreated line (p < or = 0.04). Whether an aberrant expression of beta 1 integrin receptors in resistant cells in combination with altered tumor cell adhesiveness is caused by MDR induction or whether it is an epiphenomenon of cytotoxic stress is unknown. Future studies will be needed to characterize the clinical relevance of MDR-associated changes in tumor cells.
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PMID:Exposure to vinblastine modulates beta 1 integrin expression and in vitro binding to extracellular matrix molecules in a human renal carcinoma cell line. 903 Feb 41

ELAM is an E-Selectin adhesion molecule involved in the inflammatory process but it is also thought to potentially participate in the development of blood borne metastases, by facilitating tumour cell adhesion to vessels wall. ELAM expression in tumours was immunohistochemically investigated in 203 breast carcinomas. Frozen tissue sections were probed with monoclonal anti ELAM (Clone 1.2B6) using automated and quantitative immunoperoxidase systems. A positive anti-ELAM immunoreaction was observed in 113 tumours (57%). The mean surface of positive tumours varied from 3% to 50% (mean = 11.75%, SD = 8.7) and was correlated with histoprognostic indicators and tumour expression of various antigens detected according to the same method as ELAM. The results showed that ELAM immunoexpression was independent of the tumour size, grade and type and of the nodal status but significantly increased parallel to patients' age (p<0. 01). ELAM expression was independent of Ki-67/MIB1, anti-P53 and anti-Bcl2, anti-CD44v, anti-c-erbB-2, anti-CD31, anti-RE/RP, anti-PS2, and anti-VLA3 immunoreactions. But ELAM expression correlated with that of the VCAM vascular cell adhesion molecule (p=0.0004), VLA2 (p<0.0001), P-glycoprotein (p=0.025), and of Cathepsin D to a lower degree (p=0.06) and inversely correlated with E-cadherin (p=0.03). The results suggest that endothelial cell activation is independent of tumour cell proliferative activity and of stromal angiogenesis and that the precise role and regulation of ELAM in tumours remains to be elucidated. Also the clinical relevance of ELAM immunohistochemical expression requires further investigation and correlation with patients' follow-up.
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PMID:ELAM selectin expression in breast carcinomas detected by automated and quantitative immunohistochemical assays. 953 26

VLA2 is thought to be involved in the metastatic process in malignant tumours, in particular in carcinomatous cell adhesion to vessel basement membrane. VLA2 expression was immunohistochemically investigated in 204 breast carcinomas. Frozen tissue sections were probed with monoclonal anti-VLA2 using automated (Ventana ES 320 System) and quantitative (SAMBA 2005 image processor) immunoperoxidase. A positive anti-VLA2 immunoreaction was observed in 48 tumours (23.5%), within epithelial carcinomatous cells. The VLA2-positive surface in tumours varied from 3% to 20% (mean 8.75, S.D. 7.17) and was correlated with histoprognostic indicators and tumour expression of various antigens detected using the same method as that for VLA2. The results show that VLA2 immunoexpression was independent of the tumour size, grade, type and aneuploidy, and of the nodal status. VLA2 significantly correlated with ELAM, VCAM, VLA3 and P-glycoprotein (P-gp) (P < 0.01) and inversely correlated with cathepsin D (P < 0.001), but was independent of Ki67/MIB1, p53, bcl-2, c-erbB-2, E cadherin, CD44v, CD31, oestrogen and progesterone receptors' (ER, PR) antigenic sites and pS2. The exact role, if any, of VLA2 in tumour cell dissemination remains to be elucidated and the clinical relevance of VLA2 immunodetection in breast carcinomas requires further investigation of the correlation between VLA2 immunocytochemical expression and patients' outcome and response to chemotherapy.
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PMID:VLA2 integrin expression in breast carcinomas evaluated by automated and quantitative immunohistochemistry. 964 45

A number of studies have reported that increased P-glycoprotein expression in drug-resistant tumour cells may be associated with decreased expression of a family of surface glycoproteins. However, despite its potential biological and clinical relevance, this phenomenon has not been extensively studied. In this study the phenotypic alterations that are associated with the acquisition of the multidrug-resistant phenotype in tumour cells, together with drug transporter overexpression, were investigated in human melanoma cells. The expression of cell adhesion molecules was analysed in a panel of multidrug-resistant melanoma cell lines (M14Dx) showing different degrees of resistance to doxorubicin and different levels of the expression of the drug transporter P-glycoprotein. In particular, expression of intercellular adhesion molecule-1 (ICAM-1), CD44, very late activation antigen (VLA)-5 and VLA-2 was determined by flow cytometry in the different resistant cell lines. A progressive downregulation of all the adhesion molecules examined was revealed in M14Dx cells, in parallel with an increasing level of expression of the drug transporter P-glycoprotein. The results obtained raise the question of the role of P-glycoprotein in the invasive and metastatic behaviour of tumour cells.
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PMID:What is the relationship between P-glycoprotein and adhesion molecule expression in melanoma cells? 1193 Jan 6