The structural and functional analysis of cadherin calcium-dependent cell adhesion molecules

Grunwald, Gerald B.

doi:10.1016/0955-0674(93)90028-o

Cited by 265 publications

(165 citation statements)

References 49 publications

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“…The loss of E-cadherin expression, a transmembrane protein and a prominent factor in maintaining the epithelial architectural structure, has been found to be significantly associated with the syncytial growth pattern (58). Interestingly, the cytoplasmic domain of E-cadherin is closely connected to the actin skeleton network via a complex of ␣-, ␤-, and ␥-catenins (59,60). An association between BCRA1 germline mutation and syncytial growth has also been observed (61,62).…”

Section: Discussionmentioning

confidence: 86%

Translocation of an Intracellular Antigen to the Surface of Medullary Breast Cancer Cells Early in Apoptosis Allows for an Antigen-Driven Antibody Response Elicited by Tumor-Infiltrating B Cells

Hansen

Nielsen

Ditzel

2002

The Journal of Immunology

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Tumor-infiltrating lymphoplasmacytic cells are a key feature of medullary carcinoma of the breast (MCB), a distinct subtype of human breast cancer that, despite cytologically anaplastic characteristics, has a more favorable prognosis than other types of breast cancer. Since it has been proposed that the improved clinical outcome is due at least in part to the presence of a prominent lymphoplasmacytic cell infiltrate in the tumor stroma, we recently examined the tumor-infiltrating B cell response in MCB and showed that it is oligoclonal and directed against an intracellular protein translocated to the cell surface upon MCB cell apoptosis. Human Abs cloned from MCB lymphoplasmacytic infiltrate-derived phage display libraries and reflecting the dominant part of the response were used to identify the target Ag as actin. Here, we have characterized in detail the cloned human IgG Abs and the translocation process of actin to the cell surface of apoptotic MCB cells. Our analysis shows that the cloned Abs bind specifically and with high affinity to actin, as determined by ELISA and surface plasmon resonance. Sequence analysis revealed that the Abs are highly somatically mutated, with high replacement to silent ratios, indicative of an Ag-driven, affinity-matured response. Interestingly, the tumor-infiltrating B cells in half the MCB patients mainly exhibited an IgG2 response, while IgG1 dominated in the others. To gain insight to the molecular events that may elicit such an Ab response, we examined the translocation of actin to the cell surface of apoptotic MCB cells using flow cytometry and laser scanning cytometry. Our results show that actin becomes exposed on the cell surface of a large proportion of apoptotic MCB cells as an early apoptotic event. We propose that the Ab response against actin produced by tumor-infiltrating B lymphoplasmacytic cells is Ag-driven, affinity-matured, and elicited due to the increased rate of apoptosis occurring within the MCB tumor that facilitates the translocation and proteolytic fragmentation of intracellular proteins.

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Section: Discussionmentioning

confidence: 86%

Translocation of an Intracellular Antigen to the Surface of Medullary Breast Cancer Cells Early in Apoptosis Allows for an Antigen-Driven Antibody Response Elicited by Tumor-Infiltrating B Cells

Hansen

Nielsen

Ditzel

2002

The Journal of Immunology

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“…26 The E-cadherin/catenin complex is important for cellular polarity, maintenance of normal tissue morphology and cellular differentiation. 27 Loss of E-cadherinmediated cell adhesion is involved in tumor progression and metastasis. There is also evidence that E-cadherin may have a role in invasion suppression.…”

Section: Discussionmentioning

confidence: 99%

E-cadherin expression in plasmacytoid, signet ring cell and micropapillary variants of urothelial carcinoma: comparison with usual-type high-grade urothelial carcinoma

et al. 2011

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Loss of E-cadherin expression has been linked to the invasive phenotypes of a variety of neoplasms, including lobular breast cancer. The expression of E-cadherin in variants of urothelial carcinoma relative to usual-type urothelial carcinoma, maximum depth of invasion and angiolymphatic invasion has not been well characterized. A total of eight cases of micropapillary urothelial carcinoma, four cases of plasmacytoid urothelial carcinoma, two cases of urothelial carcinoma with signet ring cell differentiation and two cases of urothelial carcinoma with mixed plasmacytoid and signet ring cell differentiation, all obtained from cystectomy/cystoprostatectomy cases, were identified. In all nine cases of usual-type invasive and noninvasive high-grade urothelial carcinoma were also included in the study. Immunohistochemical staining of E-cadherin was performed in all cases. Pathological parameters including depth of invasion and presence of angiolymphatic invasion were documented. Maximum depth of invasion: In micropapillary urothelial carcinoma, extravesical extension was seen in three of eight cases; muscularis propria invasion in four of eight cases; and lamina propria invasion in one of eight cases. In plasmacytoid urothelial carcinoma, extravesical extension was observed in two of four cases, and muscularis propria invasion and lamina propria invasion in one of four cases each. In urothelial carcinoma with signet ring cell differentiation, extravesical extension and muscularis propria invasion was seen in one of two cases each. In urothelial carcinoma with mixed plasmacytoid and signet ring cell differentiation, muscularis propria invasion and lamina propria invasion was observed in one of two cases each. In usual-type high-grade urothelial carcinoma, extravesical extension was seen in six of nine cases and noninvasive in three of nine cases. In angiolymphatic invasion, micropapillary urothelial carcinoma was observed in eight of eight cases; plasmacytoid urothelial carcinoma in two of four cases; urothelial carcinoma with signet ring cell differentiation in one of two cases; and urothelial carcinoma with mixed plasmacytoid and signet ring cell differentiation in one of two cases. Usual-type high-grade urothelial carcinoma was seen in six of nine cases. E-cadherin expression: All eight cases of micropapillary urothelial carcinoma were positive for E-cadherin in the micropapillary component and adjacent usual-type urothelial carcinoma. The four cases of plasmacytoid urothelial carcinoma, two cases of urothelial carcinoma with signet ring cell differentiation and two cases of urothelial carcinoma with mixed plasmacytoid and signet ring cell differentiation were all negative for E-cadherin. All nine additional cases of usual-type high-grade urothelial carcinoma were diffusely positive for E-cadherin. E-cadherin is diffusely positive in usual-type urothelial carcinoma and micropapillary urothelial carcinoma, irrespective of pathological stage and angiolymphatic invasion. Loss of E-cadherin expression may be a marker of...

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“…They rely on Ca 2þ ions to maintain their elongated structure and enable their adhesive functions (4)(5)(6)(7)(8). The normal physiological extracellular calcium level is 2.12-2.62 mM; with~40% of the Ca 2þ ions binding to proteins and~10% of them bound to various anions in complexes, the corresponding free calcium level is 1.16-1.31 mM (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Cadherin Diffusion in Supported Lipid Bilayers Exhibits Calcium-Dependent Dynamic Heterogeneity

Cai

Shashikanth

Leckband

et al. 2016

Biophysical Journal

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Ca 2þ ions are critical to cadherin ectodomain rigidity, which is required for the activation of adhesive functions. Therefore, changes in Ca 2þ concentration, both in vivo and in vitro, can affect cadherin conformation and function. We employed single-molecule tracking to measure the diffusion of cadherin ectodomains tethered to supported lipid bilayers at varying Ca 2þ concentrations. At a relatively high Ca 2þ concentration of 2 mM, cadherin molecules exhibited a fast diffusion coefficient that was identical to that of individual lipid molecules in the bilayer (D fast z 3 mm 2 /s). At lower Ca 2þ concentrations, where cadherin molecules were less rigid, the ensemble-average cadherin diffusion coefficient was systematically smaller. Individual cadherin trajectories were temporally heterogeneous, exhibiting alternating periods of fast and slow diffusion; the periods of slow diffusion (D slow z 0.1 mm 2 /s) were more prevalent at lower Ca 2þ concentration. These observations suggested that more flexible cadherin ectodomains at lower Ca 2þ concentration alternated between upright and lying-down conformations, where the latter interacted with more lipid molecules and experienced greater viscous drag.

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The structural and functional analysis of cadherin calcium-dependent cell adhesion molecules

Cited by 265 publications

References 49 publications

Translocation of an Intracellular Antigen to the Surface of Medullary Breast Cancer Cells Early in Apoptosis Allows for an Antigen-Driven Antibody Response Elicited by Tumor-Infiltrating B Cells

Translocation of an Intracellular Antigen to the Surface of Medullary Breast Cancer Cells Early in Apoptosis Allows for an Antigen-Driven Antibody Response Elicited by Tumor-Infiltrating B Cells

E-cadherin expression in plasmacytoid, signet ring cell and micropapillary variants of urothelial carcinoma: comparison with usual-type high-grade urothelial carcinoma

Cadherin Diffusion in Supported Lipid Bilayers Exhibits Calcium-Dependent Dynamic Heterogeneity

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