Characterization of a Novel Human Type II Epithelial Keratin K1b, Specifically Expressed in Eccrine Sweat Glands

Langbein, Lutz; Rogers, Michael A.; Praetzel, Silke; Cribier, B.; Peltre, Bernard; Gaßler, Nikolaus; Schweizer, Jürgen

doi:10.1111/j.0022-202x.2005.23860.x

Cited by 67 publications

(85 citation statements)

References 62 publications

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“…Based on a detailed keratin expression study, we have recently shown that in the duct of eccrine sweat glands the differentiation processes in both the peripheral and, in particular, the luminal cell layer start very early, already within the lowermost, intraglandular portion of the duct (14). In line with this, Fig.…”

Section: K801 Expression In Other Epithelialsupporting

confidence: 58%

“…As these glycine-rich loops are not present in the K80 molecule, the function of the keratin must lie elsewhere. There are a few examples where the cells of epithelial structures such as the companion layer (13), the cuticle of the hair follicle, 3 or the luminal layer of the eccrine sweat gland duct (14) gain unilateral strengthening through the asymmetric accumulation of most of their keratin IFs. We believe that the way K80 IFs are tightly interwoven into the binding area of cytoplasmic keratin IFs at desmosomes along the entire cell membrane represents an ideal means to uniformly stabilize the latter to render it able to cope with the high cellular deformability provided by the glycine loops present in internal keratin IFs.…”

Section: Discussionmentioning

confidence: 99%

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Against the Rules: Human Keratin K80

Langbein

Eckhart

Rogers

et al. 2010

Journal of Biological Chemistry

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Of the 54 human keratins, five members have, at present, only been characterized at the gene level. In this study we have investigated the expression patterns of keratin K80, whose gene is located at the centromeric end of the type II keratin gene domain. K80 possesses a number of highly unusual properties. Structurally, it is distinctly closer to type II hair keratins than to type II epithelial keratins. Nonetheless, it is found in virtually all types of epithelia (stratified keratinizing/non-keratinizing, hard-keratinizing, as well as non-stratified tissues, and cell cultures thereof). This conspicuously broad expression range implies an unprecedented in vivo promiscuity of K80, which involves more than 20 different type I partners for intermediate filament (IF) formation. Throughout, K80 expression is related to advanced tissue or cell differentiation. However, instead of being part of the cytoplasmic IF network, K80 containing IFs are located at the cell margins close to the desmosomal plaques, where they are tightly interlaced with the cytoplasmic IF bundles abutting there. In contrast, in cells entering terminal differentiation, K80 adopts the "conventional" cytoplasmic distribution. In evolutionary terms, K80 is one of the oldest keratins, demonstrable down to fish. In addition, KRT80 mRNA is subject to alternative splicing. Besides K80, we describe a smaller but fully functional splice variant K80.1, which arose only during mammalian evolution. Remarkably, unlike the widely expressed K80, the expression of K80.1 is restricted to soft and hard keratinizing epithelial structures of the hair follicle and the filiform tongue papilla.At present, of the 54 human keratins, only five members, i.e. the type I keratins K23, K24, and the type II keratins K78, K79, and K80 (1-3), have been characterized essentially at the gene/cDNA level, whereas detailed studies on the expression of the respective mRNAs and their proteins in human epithelia are still missing. To close this gap, we set out to investigate the expression characteristics of the type II keratin K80 (previously designated Kb20 (4)). Earlier bioinformatic analyses have shown that the KRT80 gene is located at the centromeric end of the human type II keratin gene domain on chromosome 12q13.13 (Fig. 1A). The isolated K80 cDNA encodes a 452-amino acid protein with a calculated molecular mass of 50.5 kDa and an isoelectric point of 5.47 (2).Remarkably, ␣-helical rod domain-based evolutionary analyses of the 26 type II keratins revealed a conspicuously long branch length for K80, thus indicating a relatively low homology of its ␣-helix to those of the remaining type II epithelial keratins, whereas its sequence affinity to type II hair keratins was relatively high (Fig. 1B, and Ref. 2). This was also reflected in the non-␣-helical K80 end domains that contained a relatively high number of proline and cysteine residues along with the complete absence of GGG or GGX repeats (2), typically found in the head and tail domains of most type II epithelial keratins (Fig....

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Section: K801 Expression In Other Epithelialsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Against the Rules: Human Keratin K80

Langbein

Eckhart

Rogers

et al. 2010

Journal of Biological Chemistry

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“…K1b antibody is specific for cytokeratin 77 (CK77), selectively expressed in the eccrine excretory sweat duct. 4 Taken altogether, histological and immunohistochemical data were suggestive of an original and previously undescribed eccrine nevus (EN), with abnormal eccrine structures and a prominent angiomyxoid concentric stroma, for which we propose the descriptive name ''angiomyxoid eccrine nevus. ''…”

Section: Immunohistochemical Findingsmentioning

confidence: 87%

“…Remarkably, CK77 is highly specific of the luminal cells of the eccrine excretory duct. 4 It is not only absent from the duct of apocrine sweat glands and sebaceous glands but also from other secretory glands of the body. 4 CEA is known to be positive in the luminal cells of the secretory and excretory parts of the eccrine sweat gland.…”

Section: Discussionmentioning

confidence: 99%

A Unique Presentation of Eccrine Hamartoma: Eccrine Nevus With Abnormal Eccrine Structures and Angiomyxoid Stroma

Battistella

Fraïtag²,

Cribier³

2009

The American Journal of Dermatopathology

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Eccrine hamartomas are very rare lesions usually presenting in early childhood, with variable clinical presentations. Local hyperhidrosis is often noticed. These lesions are all characterized by an increase in number and/or size of normal eccrine glands. We report the case of a hamartomatous lesion composed of eccrine structures and prominent angiomyxoid stroma, diagnosed in a 9-year-old girl. In this lesion, eccrine structures were not normal eccrine coils or ducts but ramified strands of small eosinophilic cells, containing a few eccrine ducts. These epithelial structures expressed carcinoembryonic antigen, cytokeratin 14, and cytokeratin 77, in a pattern suggesting ductal eccrine differentiation. The mesenchymatous component contained numerous capillary vessels in an abundant myxoid stroma. It was organized concentrically around the epithelial structures. This angiomyxoid stroma was somewhat reminiscent of mucinous eccrine nevi and eccrine angiomatous hamartomas. We propose to describe this unique lesion inside the group of eccrine nevi with the term "angiomyxoid eccrine nevus."

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“…31 Primary antibodies: rat mAb anti mouse CD31 (Becton Dickinson, Heidelberg, Germany), guinea pig anti pan-keratin (Progen, Heidelberg, Germany), bisbenzimide (Hoechst, Invitrogen, Darmstadt, Germany), rabbit mAB anti Ki67 (Progen), guinea pig anti Loricrin, guinea pig anti K10 (kindly provided by L. Langbein 32 ), rabbit anti ColIV (Progen). Stained sections were photographed using the Leica DM RBE fluorescence microscope (Leica, Wetzlar, Germany) and further analyzed with Cell Software (Olympus, Hamburg, Germany).…”

Section: Immunomorphological Analysismentioning

confidence: 99%

Effects of selective MMP-13 inhibition in squamous cell carcinoma depend on estrogen

et al. 2014

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Matrix metalloproteinases like MMP-13 cleave and remodel the extracellular matrix and thereby play a crucial role in tumor progression in vivo. Using a highly selective inhibitor to block MMP-13 protein activity, we demonstrate a striking inhibitory effect on invasive tumor growth and vascularization in murine skin squamous cell carcinoma (SCC). Therapy outcome critically depends on animal age in C57Bl/6 mice and was successful in old female but not in young female mice. Treatment success was recovered by ovariectomy in young and abolished by 17ß-estradiol supplementation in old mice, suggesting a hormone dependent inhibitor effect. Responsiveness of the tumorigenic keratinocytes BDVII and fibroblasts to 17ß-estradiol was confirmed in vitro, where MMP-13 inhibitor treatment led to a reduction of cell invasion and vascular endothelial growth factor (VEGF) release. This correlated well with a less invasive and vascularized tumor in treated mice in vivo. 17ß-estradiol supplementation also reduced invasion and VEGF release in vitro with no additional reduction on MMP-13 inhibitor treatment. This suggests that low 17ß-estradiol levels in old mice in vivo lead to enhanced MMP-13 levels and VEGF release, allowing a more effective inhibitor treatment compared to young mice. In our study, we present a strong link between lower estrogen levels in old female mice, an elevated MMP-13 level, which results in a more effective MMP-13 inhibitor treatment in fibroblasts and SCC cells in vitro and in vivo.Matrix metalloproteinases (MMPs) are a family of structurally related zinc dependent endopeptidases 1 that contribute to physiological remodeling of the extracellular matrix (ECM) in embryonic development, wound healing and angiogenesis. 2Beyond that, MMPs are involved in pathological conditions, including chronic wounds, rheumatoid arthritis and cancer. In cancer, they show host protective functions like cleavage and inactivation of chemokines that mediate organ-specific metastasis 3,4 and are involved in enhancing bioavailability and activation of cytokines and chemokines. This includes the release of vascular endothelial growth factor (VEGF) from the matrix, leading to an induction of angiogenesis in vivo.5,6 Among the MMPs, collagenases (MMP-1, MMP-8 and MMP-13) play an important role in tumor invasion and metastasis due to their ability to degrade native fibrillar collagen. 7 Human collagenase 1 (hMMP-1) is expressed by keratinocytes, fibroblasts, endothelial cells and others under physiological conditions. 1 In numerous tumors like breast, gastric and oesophageal carcinoma, it is associated with tumor progression or poor clinical outcome and serves as tumor marker in vivo.8-11 Expression of human collagenase-3 (hMMP-13) is associated with invasion and metastasis in a variety of malignant tumors [breast, squamous cell carcinomas (SCCs), HNSCCs and melanomas] 12-15 where it is found in tumor cells, but also in stromal cells. [16][17][18] Tumor progression is mediated by a crosstalk between tumor and stromal cells like fibr...

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Characterization of a Novel Human Type II Epithelial Keratin K1b, Specifically Expressed in Eccrine Sweat Glands

Cited by 67 publications

References 62 publications

Against the Rules: Human Keratin K80

Against the Rules: Human Keratin K80

A Unique Presentation of Eccrine Hamartoma: Eccrine Nevus With Abnormal Eccrine Structures and Angiomyxoid Stroma

Effects of selective MMP-13 inhibition in squamous cell carcinoma depend on estrogen

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