MUC1 mucin and carbohydrate associated antigens as tumor markers in head and neck squamous cell carcinoma

Croce, María Virginia; Rabassa, Martín Enrique; Price, M.R.; Segal‐Eiras, Amada

doi:10.1007/bf03032385

Cited by 34 publications

(32 citation statements)

References 26 publications

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“…The murine anti-Tn mAb (clone 83D4, IgM) recognized tumor cells from human carcinomas tissue sections but not the surrounding normal tissue (14,15,22). 83D4 strongly labelled more than 80% of ovarian and breast cancers (X. Sastre-Garau, unpublished results).…”

Section: Resultsmentioning

confidence: 99%

“…The Tn epitope (GalNAc-OSerine/Threonine) is a cryptic determinant not detectable in normal cells, because it is masked by other sugar residues on mature saccharide chains. Aberrant protein glycosylation processes occur in almost 90% of human carcinomas (13)(14)(15)(16)(17)(18), causing incomplete elongation of carbohydrate chains and unmasking the Tn antigen. Thus, Tn is one of the most widely expressed and specific tumor-associated antigens described so far, representing an attractive target for antibody-mediated passive immunotherapy (1,2).…”

Section: Introductionmentioning

confidence: 99%

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Antibody-Dependent Cell Cytotoxicity Synapses Form in Mice during Tumor-Specific Antibody Immunotherapy

et al. 2011

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Antibody-dependent cell cytotoxicity (ADCC) plays a critical role in monoclonal antibody (mAb)-mediated cancer therapy. ADCC, however, has not been directly shown in vivo but inferred from the requirement for IgG Fc receptors (FcgR) in tumor rejection in mice. Here, we investigated the mechanism of action of a Tn antigenspecific chimeric mAb (Chi-Tn), which binds selectively to a wide variety of carcinomas, but not to normal tissues, in both humans and mice. Chi-Tn mAb showed no direct toxicity against carcinomas cell lines in vitro but induced the rejection of a murine breast tumor in 80% to 100% of immunocompetent mice, when associated with cyclophosphamide. Tumor rejection was abolished in Fc receptors-associated g chain (FcR-g)-deficient mice, suggesting a role for ADCC. Indeed, tumor cells formed stable conjugates in vivo with FcR-g chainexpressing macrophages and neutrophils in Chi-Tn mAb-treated but not in control mAb-treated mice. The contact zone between tumor cells and ADCC effectors accumulated actin, FcgR and phospho-tyrosines. The in vivo formed ADCC synapses were organized in multifocal supra-molecular activation clusters. These results show that in vivo ADCC mediated by macrophages and neutrophils during tumor rejection by Chi-Tn mAb involves a novel type of multifocal immune synapse between effectors of innate immunity and tumor cells. Cancer Res; 71(15); 5134-43. Ó2011 AACR.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antibody-Dependent Cell Cytotoxicity Synapses Form in Mice during Tumor-Specific Antibody Immunotherapy

et al. 2011

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“…The marked increase in CD3 + , CD68 + and TIA-1 + cells, with the development of the keratinocytic hyperproliferative lesions (non-tumorigenic, AK and SCC) may be due to increase in the load of associated antigens on these damaged keratinocytes. In the pretumorigenic and tumorigenic lesions (AK and SCC), these antigens possibly include core protein of MUCI and associated carbohydrate antigens, 7 and cancer/testis antigens. 8 Alternatively, in the nontumorigenic lesions, these antigens include the viral antigens such as human papillomavirus antigens (VV), bacterial superantigens (LP), HLA antigens, cutaneous lymphocyte-associated antigen (PV).…”

Section: Discussionmentioning

confidence: 99%

Analysis of the mononuclear inflammatory cell infiltrate in the nontumorigenic, Pretumorigenic and tumorigenic keratinocytic hyperproliferative lesions of the skin

Hussein¹,

Ahmed²

2005

Cancer Biology & Therapy

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Background: The keratinocytic hyperproliferative lesions include non-tumorigenic, pre-tumorigenic (actinic keratoses, AK), and tumorigenic (squamous cell carcinomas, SCC) conditions. Although mononuclear inflammatory cell infiltrate (MICs) is a constant feature in these lesions, their immunophenotypic characterization is still incomplete. We hypothesized that the development of non-tumorigenic, pre-tumorigenic, and tumorigenic keratinocytic hyperproliferative lesions is associated with alterations in the mononuclear inflammatory cell infiltrate in response to altered antigenicity of the lesional cells. This study tries to test this hypothesis and to characterize MICs in these lesions.Methods: Fifty lesions (non-tumorigenic lesions, 29; AK, 9 and SCC, 12) were examined using immunoperoxidase staining methods and antibodies targeting histiocytes (CD68), T cells (CD3), B cells (CD20), and T cells with cytotoxic potential (TIA-1).Results: As compared to the normal skin, the development of the keratinocytic hyperproliferative lesions (normal skin; non-tumorigenic; AK and SCC) was associated with a statistically significant increase(p = <0.05) in: (1) CD20 + B lymphocytes (0.0 ± 0.0 vs. 3.1 ± 0.5 vs. 7.5 ± 0.3 vs. 14.5 ± 5.5); (2) CD68 histiocytes (4.0 ± 1.0 vs. 26.5 ± 3.9 vs. 23 ± 1.9 vs. 41.3 ± 6.8); (3) CD3 + T lymphocytes (3.0 ± 1.1 vs. 58.3 ± 10.3 vs. 54.5 ± 0.2 vs. 41.0 ± 16.0); and (4) TIA-1 + cytotoxic T cells (1.8 ± 0.4 vs. 2.9 ± 0.7 vs. 9.6 ± 1.1 vs. 13.7 ± 5.2).Conclusions: The increase in the number of infiltrating mononuclear cells in all pathologic lesions compared to normal skin may reflect increased antigenicity of the lesional cells. Both humoral and cell mediated immunity are involved in these lesions.

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“…They did not look at MUC2. The same group a year later reported on their Wndings of detecting a very low level of MUC1 in seven normal specimens (no value given) and in 6/8 of SCC specimens [18]. Again, this study suggested that MUC1 was increased in SCC specimens as compared to normal specimens.…”

Section: Discussionmentioning

confidence: 71%

“…A year later, the same group reported on MUC1 mucin and carbohydrate associated antigens as tumour markers in head and neck squamous cell carcinoma (HNSCC) [18]. They studied specimens from 29 patients with tumour found in tongue (10), larynx (8), oral cavity (4), maxillary sinus (3), tonsillar ring (3) and pharynx (1) using immunohistochemistry and Western blotting.…”

Section: Resultsmentioning

confidence: 98%

What role do mucins have in the development of laryngeal squamous cell carcinoma? A systematic review

Sipaul

Birchall

Corfield

2011

Eur Arch Otorhinolaryngol

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Mucins are the dominant component in the protective mucus layer on mucosal surfaces including the larynx. Hence, they are part of the first line of defence against external stimuli including effect of smoking in the larynx. We asked whether existing published evidence supported the hypothesis that alteration in mucins expression/production is related to the laryngeal neoplastic process. The objective of this study is to review published evidence for mucins having an important role in normal laryngeal physiology and the development of laryngeal squamous cell carcinoma (SCC). We aimed to review all available literature on mucins in the larynx in order to develop hypotheses to be tested by future research. Thereby, new potential means of prevention and treatment of laryngeal cancer may be developed. A systematic search of all published literature was conducted. Systematic searches were done in the following databases: AMED, BNI, EMBASE, HMIC, MEDLINE, PsycINFO, CINAHL and HEALTH BUSINESS ELITE from their respective inception up to 11 February 2011. The following keywords were used in combination: mucin, larynx and squamous cell carcinoma. Altogether, 53 studies were identified; 43 studies were excluded following screening of the titles and abstracts. Full text manuscripts for ten studies were obtained for detailed evaluation and five studies were included in this review. No single study fulfilled all relevant criteria. Based on the included studies, we now know that MUC1 is definitely expressed in SCC larynx. However, there is no definitive evidence to suggest that MUC1 and MUC2 are aberrantly expressed in SCC larynx as compared to normal larynx. Further studies using the best available detection technique to detect MUC1, MUC2 and other possible relevant mucins i.e., MUC4 on adequate numbers of normal and SCC specimens are needed to confirm the findings of this review.

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MUC1 mucin and carbohydrate associated antigens as tumor markers in head and neck squamous cell carcinoma

Abstract: 1) head and neck carcinoma expressed MUCI and associated carbohydrate antigens in high levels; 2) no relationship between antigenic expression and tumor status was found.

Cited by 34 publications

References 26 publications

Antibody-Dependent Cell Cytotoxicity Synapses Form in Mice during Tumor-Specific Antibody Immunotherapy

Antibody-Dependent Cell Cytotoxicity Synapses Form in Mice during Tumor-Specific Antibody Immunotherapy

Analysis of the mononuclear inflammatory cell infiltrate in the nontumorigenic, Pretumorigenic and tumorigenic keratinocytic hyperproliferative lesions of the skin

What role do mucins have in the development of laryngeal squamous cell carcinoma? A systematic review

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