A study of desmosomes in colorectal carcinoma

Collins, Jane; Taylor, Ian W.; Garrod, David R.

doi:10.1038/bjc.1990.382

Cited by 31 publications

(19 citation statements)

References 52 publications

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“…However, it should be noted that in some cases it appears that Dsc2 expression is lost in the presence of normal amounts of E-cadherin (Supplementary Table 3). No reduction in desmocollin expression was found in the only previous study of desmosomes in colorectal cancer (Collins et al, 1990). The most likely explanation for the discrepancy lies in the antibodies used.…”

Section: Discussionmentioning

confidence: 74%

“…These changes in Dsc expression pattern may result in significant alterations in desmosome function, but do not result in the complete loss of desmosomes from colorectal cancer tissue (Collins et al, 1990). However, it is possible that the size and number of desmosomes is reduced (Bosch et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…We have been careful to use antibodies specific for individual Dsc isoforms. Collins et al (1990) carried out their study before all of the desmocollin isoforms had been discovered and their antibody may have reacted with more than one isoform.…”

Section: Discussionmentioning

confidence: 99%

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Desmocollin switching in colorectal cancer

et al. 2006

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The desmocollins are members of the desmosomal cadherin family of cell -cell adhesion molecules. They are essential constituents of desmosomes, intercellular junctions that play a critical role in the maintenance of tissue integrity in epithelia and cardiac muscle. In humans, three desmocollins (Dsc1, Dsc2 and Dsc3) have been described. The desmocollins exhibit tissue-specific patterns of expression; only Dsc2 is expressed in normal colonic epithelium. We have found switching between desmocollins in sporadic colorectal adenocarcinoma with a reduction in Dsc2 protein (in 8/16 samples analysed by immunohistochemistry) being accompanied by de novo expression of Dsc1 (16/16) and Dsc3 (7/16). Similar results were obtained by western blotting of a further 16 samples. No change was found in Dsc2 mRNA, but de novo expression of Dscs 1 and 3 was accompanied by increased message levels. Loss of Dsc2

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Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

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Desmocollin switching in colorectal cancer

et al. 2006

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“…By contrast, the desmosomes of cells in confluent culture become resistant to disruption even by divalent cation chelation. This has been demonstrated for keratinocytes, MadinDarby canine kidney (MDCK) cells, and two colorectal carcinoma cell lines (Watt et al, 1984;Mattey and Garrod, 1986b;Collins et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

The α Isoform of Protein Kinase C Is Involved in Signaling the Response of Desmosomes to Wounding in Cultured Epithelial Cells

Wallis

Lloyd

Wise

et al. 2000

MBoC

158

211

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Initiation of reepithelialization upon wounding is still poorly understood. To enhance this understanding, we focus here on changes in the adhesive state of desmosomes of cultured Madin-Darby canine kidney cells in response to wounding of confluent cell sheets. Previous results show that desmosomal adhesion in Madin-Darby canine kidney cells changes from a calcium-dependent state to calcium independence in confluent cell sheets. We show that this change, which requires culture confluence to develop, is rapidly reversed upon wounding of confluent cell sheets. Moreover, the change to calcium dependence in wound edge cells is propagated to cells hundreds of micrometers away from the wound edge. Rapid transition from calcium independence to calcium dependence also occurs when cells are treated with phorbol esters that activate PKC. PKC inhibitors, including the conventional isoform inhibitor Gö 6976, cause rapid transition from calcium dependence to calcium independence, even in subconfluent cells. The cellular location of the ␣ isoform of PKC correlates with the calcium dependence of desmosomes. Upon monolayer wounding, PKC␣ translocates rapidly to the cell periphery, becomes Triton X-100 insoluble, and also becomes concentrated in lamellipodia. The PKC␣ translocation upon wounding precedes both the increase in PKC activity in the membrane fraction and the reversion of desmosomes to calcium dependence. Specific depletion of PKC␣ with an antisense oligonucleotide increases the number of cells with calcium-independent desmosomes. These results show that PKC␣ participates in a novel signaling pathway that modulates desmosomal adhesion in response to wounding.

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“…[32][33][34][35][36][37] However, some reports showed unchanged staining of these components in a variety of tumors, suggesting that loss of demosomes is not necessary for tumor invasion and metastasis. 38,39 In carcinomas, mutations of genes encoding for desmosomal proteins have not been reported. Significantly, mutations in desmosomal genes are associated with some very severe skin diseases but not with cancer.…”

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confidence: 99%

E‐cadherin is a selective and strongly dominant prognostic factor in squamous cell carcinoma: A comparison of E‐cadherin with desmosomal components

Bosch

Andl

Abel

et al. 2005

Intl Journal of Cancer

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E-cadherin-mediated and desmosomal cell-cell adhesion have been implicated in the suppression of invasive and metastatic behavior of squamous cell carcinomas. Whether the adhaerens junction represented by E-cadherin and the desmosomes interplay or have distinct and separate roles in squamous cell cancer progression is still unclear. We have studied a cohort of 200 primary tumors and 56 lymph node metastases from different anatomic sites of the head and neck region for changes in synthesis of E-cadherin, desmoplakin and desmoglein by immunohistochemistry (IHC). Selected cases were studied by indirect immunofluorescence (IIF) and electron microscopy (EM). Only frozen sections were evaluated since they gave stronger and reproducible staining results. IHC data obtained were compared to clinical parameters. While some reduction in immunostaining was found in virtually all invasive tumors, at least partial expression, including that of E-cadherin, persisted in most late stage tumors and in lymph node metastases. Reduced desmosomal staining correlated with desmosomes reduced in numbers, size or in structural defects by EM analysis. By univariate analysis, reduction in synthesis of both E-cadherin and the desmosomal components that were generally linked (i.e., they showed positive rank correlations) were significantly associated with clinical parameters including overall and disease-free survival. However, by multivariate analysis including a Cox proportional hazards regression model (backward selection), the desmosomal components were not significant as independent prognostic factors. By contrast, E-cadherin was strongly associated with patient prognosis. In line with the highly significant association of reduced E-cadherin synthesis with an increased relative risk of follow up events, i.e., regional lymph node (p ‫؍‬ 0.0007) and distant metastasis (p < 0.0001), as well as local recurrences (p < 0.0001), the prognostic strength of E-cadherin was independent of and stronger than histological grading, N stage, tumor site, and even stronger than the TNM stage. Based on these results, evaluation of E-cadherin in squamous cell carcinomas by immunostaining is recommended as a significant prognostic marker. © 2004 Wiley-Liss, Inc.Key words: E-cadherin; cell adhesion; desmosomes; prognosis; squamous cell cancer Organization and function of epithelia depends on the integrity of junctional structures. 1,2 Among them the 2 types of "adhering junctions", i.e., the adhaerens junctions and the desmosomes contribute to intercellular adhesion and tissue stability. Key elements in intercellular adhesion are transmembrane glycoproteins of the cadherin family. The "classical" E-cadherin (ecad) maintains intercellular adhesion in the adhaerens junction, and the desmogleins (dg) and desmocollins (dc) are the principal cadherins of the desmosomes. [3][4][5][6][7][8][9][10][11][12][13] Regarding adhaerens junctions, numerous studies have shown that loss of adhesion can be caused by deletions or mutations, 14 -17 silencing by CpG methylatio...

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A study of desmosomes in colorectal carcinoma

Cited by 31 publications

References 52 publications

Desmocollin switching in colorectal cancer

Desmocollin switching in colorectal cancer

The α Isoform of Protein Kinase C Is Involved in Signaling the Response of Desmosomes to Wounding in Cultured Epithelial Cells

E‐cadherin is a selective and strongly dominant prognostic factor in squamous cell carcinoma: A comparison of E‐cadherin with desmosomal components

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