The Core Protein of Epican, a Heparan Sulfate Proteoglycan on Keratinocytes, Is an Alternative Form of CD44

Kugelman, Lisa C; Ganguly, Submay.; Haggerty, John G.; Weissman, Sherman M.; Milstone, Leonard M.

doi:10.1111/1523-1747.ep12616092

Cited by 65 publications

(34 citation statements)

References 44 publications

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“…directed against pan-CD44, CD44v3, CD44v5, and CD44v6, supports the notion that both epidermal keratinocytes and BCC cells predominantly synthesize CD44v3-10 (epican) Kugelman et al, 1992). The only detailed EM descriptions of the distribution of CD44 in the epidermis published previously are those by Tammi et al (1994) and especially Tuhkanen et al (1998).…”

Section: Dingemans Et Alsupporting

confidence: 71%

CD44 Is Exposed to the Extracellular Matrix at Invasive Sites in Basal Cell Carcinomas

Dingemans

Ramkema

Pals

2002

Laboratory Investigation

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SUMMARY:We have previously shown, by light microscopy, that the level of expression of CD44 (pan-CD44, CD44v3, CD44v5, and CD44v6) in human basal cell carcinomas is related to growth pattern and invasiveness (Br J Dermatol 1099;140:17-25). We have now studied the fine distribution of these CD44 isoforms in the same tumors using immunoelectron microscopy. Despite the strong differences in the level of expression in tumor areas with different growth patterns, CD44 was consistently found almost exclusively at intercellular surfaces, with a very strong predilection for widened intercellular pouches, ie, identical to the distribution in the normal epidermis. This prevalent distribution corroborates a role for CD44 in maintaining hyaluronan-filled spaces (J Histochem Cytochem 1998;46:241-248). However, the correlation between the presence of CD44 and the presence of such pouches was not absolute, indicating that other factors are involved as well. In contrast to the prevailing literature, we also found a weak but distinct labeling of cell surfaces facing the extracellular matrix. Interestingly, this appeared significantly elevated in the thinnest, most irregular, and usually most peripheral tumor cell strands, where it was associated with tumor cell protrusions and absence of a basal lamina. Thus, the CD44 ϩ protrusions were in direct contact with the extracellular matrix and apparently represented sites of invasion. The mechanisms that may contribute to a role of CD44 at these sites include binding of extracellular matrix components (notably hyaluronan) and several biologically active factors such as hepatocyte growth factor/scatter factor and matrix metalloproteinase 9. (Lab Invest 2002, 82:313-322).

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Section: Dingemans Et Alsupporting

confidence: 71%

CD44 Is Exposed to the Extracellular Matrix at Invasive Sites in Basal Cell Carcinomas

Dingemans

Ramkema

Pals

2002

Laboratory Investigation

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“…One candidate is CD44, which may be involved in the homing process of activated lymphocytes from the blood to the inflamed skin. CD44 is a cell surface glycoprotein that plays important roles in cell-cell interaction and cellmatrix interaction through its affinity for hyaluronic acid (HA) 13 . CD44 is a typical receptor for HA and it can bind with osteoponin, collagens and matrix metalloproteinases (MMPs).…”

Section: Discussionmentioning

confidence: 99%

“…CD44 is a typical receptor for HA and it can bind with osteoponin, collagens and matrix metalloproteinases (MMPs). The interaction of CD44 with its ligand regulates the lymphocyte activation and this leads to the migration of skin-homing T cells 13,14 . Another cell surface molecule CD56 was also identified as an up-regulated gene in the psoriatic PBMCs in this study.…”

Section: Discussionmentioning

confidence: 99%

A Global Gene Expression Analysis of the Peripheral Blood Mononuclear Cells Reveals the Gene Expression Signature in Psoriasis

et al. 2009

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Background: Psoriasis is a chronic inflammatory skin disease that affects approximately 1~3% of the general population. Objective: We performed cDNA microarray analysis with using the dendrimer labelling method to investigate the gene expression profile in the peripheral blood mononuclear cells (PBMCs) of psoriatic patients. Methods: The peripheral blood mononuclear cells of 5 patients with psoriasis and 8 control subjects were used in the gene expression analyses of psoriasis. Results: We identified 212 differentially expressed genes that showed at least a two-fold induction and/or reduction in psoriatic patients. Among those, 63 genes, including CD44, CD56 and IL7R, were induced, while 139 genes, including the sphingosine kinase 1 and p16-INK genes, were reduced in the psoriatic patients. Conclusion: We can speculate that these genes may have a role for the pathogenesis of psoriasis via their affecting different cellular functions. Our results suggest a possible mechanism by which activated immune cells migrate from the blood to the skin in psoriatic patients, and we provide novel putative targets for developing drugs to treat psoriasis. (Ann Dermatol 21(3) 237∼242, 2009)

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“…Western blot analysis showed that HaCaT cells express both the standard 90-kDa form and several higher molecular mass variants of CD44 (Fig. 1A), thus resembling normal human primary keratinocytes and human epidermis (3,41). Quantification of the bands showed that IL-1␤ caused a slight but consistent increase in the expression of CD44 (Fig.…”

Section: Il-1␤ Increases Cd44 Expression In Keratinocytes-becausementioning

confidence: 94%

Interleukin-1β-induced Reduction of CD44 Ser-325 Phosphorylation in Human Epidermal Keratinocytes Promotes CD44 Homomeric Complexes, Binding to Ezrin, and Extended, Monocyte-adhesive Hyaluronan Coats

Jokela¹,

Oikari²,

Takabe

et al. 2015

Journal of Biological Chemistry

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Background: Interleukin-1␤ recruits leukocytes at the site of inflammation. Results: The interleukin-1␤-induced hyaluronan coat increased monocyte binding to keratinocytes through ezrin-associated CD44 homomers, enabled by reduced serine 325 phosphorylation. Conclusion:The organization of the cell surface hyaluronan coat is controlled by phosphorylation of CD44. Significance: Interleukin-1␤ release in inflamed tissues triggers signals that increase hyaluronan-dependent leukocyte binding.

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The Core Protein of Epican, a Heparan Sulfate Proteoglycan on Keratinocytes, Is an Alternative Form of CD44

Cited by 65 publications

References 44 publications

CD44 Is Exposed to the Extracellular Matrix at Invasive Sites in Basal Cell Carcinomas

CD44 Is Exposed to the Extracellular Matrix at Invasive Sites in Basal Cell Carcinomas

A Global Gene Expression Analysis of the Peripheral Blood Mononuclear Cells Reveals the Gene Expression Signature in Psoriasis

Interleukin-1β-induced Reduction of CD44 Ser-325 Phosphorylation in Human Epidermal Keratinocytes Promotes CD44 Homomeric Complexes, Binding to Ezrin, and Extended, Monocyte-adhesive Hyaluronan Coats

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