Cell membrane-associated mucins and their adhesion-modulating property

Hilkens, John; Ligtenberg, Marjolÿn J.L.; Vos, Hans L.; Litvinov, Sergey V.

doi:10.1016/0968-0004(92)90315-z

Cited by 422 publications

(280 citation statements)

References 25 publications

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“…In malignancy MUC1 looses its polarized expression, redistributes and is expressed on the whole cell surface. The very large negatively charged extended rods 47 that form the extracellular portion of the molecule shield other cell surface molecules from their ligands. In this way MUC1 prevents the formation of cellcell contacts mediated by E-cadherin 48 or cell matrix contacts mediated by integrins.…”

Section: Discussionmentioning

confidence: 99%

Antibody-dependent cell-mediated cytotoxicity can be induced by MUC1 peptide vaccination of breast cancer patients

et al. 2001

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Key words: MUC1; breast cancer; ADCC; NK cells; vaccination; immunotherapyMUC1 is a transmembrane O-linked glycoprotein present on the apical surface of normal secretory epithelial cells. 1 The extracellular domain of MUC1 consists mainly of a variable number of tandem repeats 2 and it has a cytoplasmatic tail of 69 amino acids. 3 In the vast majority of human adenocarcinomas this protein is over-expressed and hypo-glycosylated 4 exposing an immunodominant repetitive amino acid sequence. The overproduction and secretion of MUC1 is correlated with the progression of breast, 5 ovarian 6,7 and colon 8 carcinoma. In breast cancer patients MUC1 serum levels are used to monitor therapy and for early detection of recurrences. 9,10 Proliferative responses to MUC1 and its tandem-repeat peptides have been demonstrated with peripheral blood mononuclear cells (PBMC) of patients with ovarian adenocarcinoma 11 and MUC1 specific cytotoxic T lymphocytes (CTL) have been isolated from tumor-draining lymph nodes of breast 12 and ovarian 13 cancer patients. In patients with ovarian, breast and pancreatic adenocarcinomas cytotoxic T cells can be induced that are specific for the MUC1 tandem repeat. 14,15 Recognition of MUC1 by T lymphocytes may be due to exposure of the immunogenic PDTRP region of the tandem repeat that is normally not exposed due to extensive O-glycosylation of the peptide core. The cytotoxic action of these T cells has also been described to be MHC-nonrestricted, due to crosslinkage to poorly glycosylated MUC1 tandem repeats on tumor cells. 16 Not only cellular but also humoral responses to MUC1 are found in breast, ovarian, colon and pancreatic carcinomas. [17][18][19] Moreover, the presence of immune-complexed MUC1 in breast cancer patients is related to a favorable disease outcome 20 and survival in early breast cancer patients is favorably influenced by a natural humoral immune response to MUC1. 21 These findings point to MUC1 and its repeat peptide as a target for immunotherapy of carcinomas. One possible approach is the use of MAbs against tumor-associated antigens, 22,23 another the use of tumorassociated antigens such as MUC1 as a vaccine and target for cellular and humoral immune responses.MUC1 MAbs have already been used in a number of vaccination trials as carrier molecule of radioactive elements 24,25 and recently a clinical trial has been set up with unlabeled humanized (Hu)HMFG-1 MAb for adjuvant therapy of breast cancer patients (Dr. D.W. Miles, Guy's Hospital, London). Also active vaccination trials with MUC1 tandem-repeat peptides 26 have been initiated. Recently, in 3 phase I vaccination trials executed by Dr. P.O. Livingston in the Memorial Sloan-Kettering Cancer Center, NY, breast cancer patients with no evidence of disease were repeatedly injected with a 30-mer 27,28 a 33-mer or a 106-mer MUC1 tandem repeat peptide conjugated to KLH plus adjuvant QS-21. In these patients high MUC1 IgG and IgM could be induced. 21 MAbs specific for tumor-associated antigens (TAA) can induce a complement-depende...

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Section: Discussionmentioning

confidence: 99%

Antibody-dependent cell-mediated cytotoxicity can be induced by MUC1 peptide vaccination of breast cancer patients

et al. 2001

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“…The mucin MUC-1, which is expressed at the apical cell surface of many normal secretory epithelial cells (Ho et al, 1993), contains an extra-cellular domain that extends above most other cell membrane-associated proteins (Hilkens et al, 1992;Hilkens et al, 1995). As such, MUC-1 has been suggested to prevent adhesion and to promote development of metastatic disease.…”

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confidence: 99%

MUC-1 gene is associated with prostate cancer death: a 20-year follow-up of a population-based study in Sweden

et al. 2007

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Anti-adhesion mucins have proven to play an important part in the biology of several types of cancer. Therefore, we test the hypothesis that altered expression of MUC-1 is associated with prostate cancer progression. We retrieved archival tumour tissue from a population-based cohort of 195 men with localised prostate cancer (T1a-b, Nx, M0) that has been followed for up to 20 years with watchful waiting. Semi-automated, quantitative immunohistochemistry was undertaken to evaluate MUC-1 expression. We modelled prostate cancer-specific death as a function of MUC-1 levels accounting for age, Gleason grade and tumour extent, and calculated age-adjusted and multivariate adjusted hazard ratios (HR). Men that had tumours with an MUC-intensity lower or higher than normal tissue had a higher risk of dying in prostate cancer, independent of tumour extent and Gleason score (HR 5.1 and 4.5, respectively). Adjustment for Gleason grade and tumour stage did not alter the results. Men with a Gleason score X7 and MUC-1 deviating from the normal had a 17 (RR ¼ 17.1 95% confidence interval ¼ 2.3 -128) times higher risk to die in prostate cancer compared with men with Gleason score o7 and normal MUC-1 intensity. In summary, our data show that MUC-1 is an independent prognostic marker for prostate cancer death.

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“…The present study focused on the appearance of KL-6 in pulmonary epithelial lining fluid (ELF) and plasma. KL-6, a pulmonary epithelial mucin with low molecular weight, is an integral membrane glycoprotein classified as cluster 9 (MUC1) (14,28), with an extracellular domain consisting mostly of tandem repeats of 20 amino acid sequences and a cytoplasmic tail (13). KL-6 splits off at the S-S bond near the epithelial membrane surface and becomes distributed in pulmonary ELF (13).…”

mentioning

confidence: 99%

Elevation of KL-6, a lung epithelial cell marker, in plasma and epithelial lining fluid in acute respiratory distress syndrome

Ishizaka¹,

Matsuda²,

Albertine³

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

160

149

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Elevation of KL-6, a lung epithelial cell marker, in plasma and epithelial lining fluid in acute respiratory distress syndrome. Am J Physiol Lung Cell Mol Physiol 286: L1088 -L1094, 2004. First published September 5, 2003 10.1152 10. /ajplung. 00420.2002 is a pulmonary epithelial mucin more prominently expressed on the surface membrane of alveolar type II cells when these cells are proliferating, stimulated, and/or injured. We hypothesized that high levels of KL-6 in epithelial lining fluid and plasma would reflect the severity of lung injury in patients with acute lung injury (ALI). Epithelial lining fluid was obtained at onset (day 0) and day 1 of acute respiratory distress syndrome (ARDS)/ALI by bronchoscopic microsampling procedure in 35 patients. On day 0, KL-6 and albumin concentrations in epithelial lining fluid were significantly higher than in normal controls (P Ͻ 0.001), and the concentrations of KL-6 in epithelial lining fluid (P Ͻ 0.002) and in plasma (P Ͻ 0.0001) were higher in nonsurvivors than in survivors of ALI/ARDS. These observations were corroborated by the immunohistochemical localization of KL-6 protein expression in the lungs of nonsurvivors with ALI and KL-6 secretion from cultured human alveolar type II cells stimulated by proinflammatory cytokines. Because injury to distal lung epithelial cells, including alveolar type II cells, is important in the pathogenesis of ALI, the elevation of KL-6 concentrations in plasma and epithelial lining fluid could be valuable indicators for poor prognosis in clinical ALI. alveolar type II cell; pulmonary edema; microsampling

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Cell membrane-associated mucins and their adhesion-modulating property

Cited by 422 publications

References 25 publications

Antibody-dependent cell-mediated cytotoxicity can be induced by MUC1 peptide vaccination of breast cancer patients

Antibody-dependent cell-mediated cytotoxicity can be induced by MUC1 peptide vaccination of breast cancer patients

MUC-1 gene is associated with prostate cancer death: a 20-year follow-up of a population-based study in Sweden

Elevation of KL-6, a lung epithelial cell marker, in plasma and epithelial lining fluid in acute respiratory distress syndrome

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