Stratum basale keratinocyte expression of the cell-surface glycoprotein CDCP1 during epidermogenesis and its role in keratinocyte migration

McGovern, Jacqui A.; Heinemann, Jessica; Burke, Les J.; Dawson, Rebecca; Parker, Tony J.; Upton, Zee; Hooper, John D.; Manton, Kerry J.

doi:10.1111/bjd.12119

Cited by 21 publications

(29 citation statements)

References 37 publications

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“…Incubation at 95 C for 4 minutes in 10 mmol/L Sodium Citrate buffer (pH 6.0; NuMA and vWF), or at 98 C for 20 minutes in Tris-EDTA buffer (pH 9.0; VN and IGFBP-3), were used to unmask the antigens. Immunohistochemistry was performed using the MACH 4 Universal Detection System (Biocare Medical) as described previously (21). Briefly, primary antibodies against NuMA (1:200), vWF (1:400), VN (1:300), and IGFBP-3 (1:150) were diluted in Da Vinci Green Diluent (Biocare Medical), and incubated overnight on the sections at 4 C. Positive immunoreactivity was visualized using the 3,3-diaminobenzidine (DAB; Biocare Medical) substrate, resulting in formation of a brown pigment.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Antagonists of IGF:Vitronectin Interactions Inhibit IGF-I–Induced Breast Cancer Cell Functions

Kashyap

Shooter

Shokoohmand

et al. 2016

Molecular Cancer Therapeutics

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We provide proof-of-concept evidence for a new class of therapeutics that target growth factor:extracellular matrix (GF: ECM) interactions for the management of breast cancer. Insulinlike growth factor-I (IGF-I) forms multiprotein complexes with IGF-binding proteins (IGFBP) and the ECM protein vitronectin (VN), and stimulates the survival, migration and invasion of breast cancer cells. For the first time we provide physical evidence for IGFBP-3:VN interactions in breast cancer patient tissues; these interactions were predominantly localized to tumor cell clusters and in stroma surrounding tumor cells. We show that disruption of IGF-I:IGFBP:VN complexes with L 27 -IGF-II inhibits IGF-I: IGFBP:VN-stimulated breast cancer cell migration and proliferation in two-and three-dimensional assay systems. Peptide arrays screened to identify regions critical for the IGFBP-3/-5:VN and IGF-II:VN interactions demonstrated IGFBP-3/-5 and IGF-II binds VN through the hemopexin-2 domain, and VN binds IGFBP-3 at residues not involved in the binding of IGF-I to IGFBP-3. IGFBP-interacting VN peptides identified from these peptide arrays disrupted the IGF-I:IGFBP:VN complex, impeded the growth of primary tumor-like spheroids and, more importantly, inhibited the invasion of metastatic breast cancer cells in 3D assay systems. These studies provide first-in-field evidence for the utility of small peptides in antagonizing GF:ECM-mediated biologic functions and present data demonstrating the potential of these peptide antagonists as novel therapeutics. Mol Cancer Ther; 15(7); 1602-13. Ó2016 AACR.

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Section: Immunohistochemistrymentioning

confidence: 99%

Antagonists of IGF:Vitronectin Interactions Inhibit IGF-I–Induced Breast Cancer Cell Functions

Kashyap

Shooter

Shokoohmand

et al. 2016

Molecular Cancer Therapeutics

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“…In vivo, basal epidermal keratinocytes are responsible for natural wound healing . Interestingly, immunostainings of human skin sections showed an exclusive expression of OR51B5 in suprabasal keratinocytes, whereas OR2A4/7 is expressed in suprabasal keratinocytes and basal melanocytes.…”

Section: Discussionmentioning

confidence: 99%

Two olfactory receptors—OR2A4/7 and OR51B5—differentially affect epidermal proliferation and differentiation

Tsai

Veitinger

Peek

et al. 2016

Experimental Dermatology

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Olfactory receptors (ORs), which belong to the G-protein coupled receptor family, are expressed in various human tissues, including skin. Cells in non-olfactory tissues tend to express more than one individual OR gene, but function and interaction of two or more ORs in the same cell type has only been marginally analysed. Here, we revealed OR2A4/7 and OR51B5 as two new ORs in human skin cells and identified cyclohexyl salicylate and isononyl alcohol as agonists of these receptors. In cultured human keratinocytes, both odorants induce strong Ca signals that are mediated by OR2A4/7 and OR51B5, as demonstrated by the receptor knockdown experiments. Activation of corresponding receptors induces a cAMP-dependent pathway. Localization studies and functional characterization of both receptors revealed several differences. OR2A4/7 is expressed in suprabasal keratinocytes and basal melanocytes of the epidermis and influences cytokinesis, cell proliferation, phosphorylation of AKT and Chk-2 and secretion of IL-1. In contrast, OR51B5 is exclusively expressed in suprabasal keratinocytes, supports cell migration and regeneration of keratinocyte monolayers, influences Hsp27, AMPK1 and p38MAPK phosphorylation and interestingly, IL-6 secretion. These findings underline that different ORs perform diverse functions in cutaneous cells, and thus offering an approach for the modulated treatment of skin diseases and wound repair.

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“…Formalin‐fixed, paraffin‐embedded sections (5 μm) of both human skin and HSE models were processed for IHC. Heat‐induced epitope retrieval was performed in a Decloaking Chamber ™ (Biocare Medical, Concord, CA, U.S.A.) and IHC was performed using the MACH 4 ™ Universal Detection System (Biocare Medical), as described previously . Primary antibodies against keratin 1 (1 : 500), loricrin (1 : 1000), Ki‐67 (1 : 100), KLK7 (1 : 400), DSC1 (1 : 1000), CDSN (1 : 1000), LEKTI (1 : 500) and SKALP (1 : 500) were diluted in Da Vinci Green Diluent ™ (Biocare Medical) and applied to the sections for 60 min at 37 °C or overnight at 4 °C.…”

Section: Methodsmentioning

confidence: 99%

Attenuated kallikrein‐related peptidase activity disrupts desquamation and leads to stratum corneum thickening in human skin equivalent models

et al. 2016

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Stratum basale keratinocyte expression of the cell-surface glycoprotein CDCP1 during epidermogenesis and its role in keratinocyte migration

Abstract: These findings delineate the expression of CDCP1 in human epidermal keratinocytes during epidermogenesis and demonstrate that CDCP1 is involved in keratinocyte migration.

Cited by 21 publications

References 37 publications

Antagonists of IGF:Vitronectin Interactions Inhibit IGF-I–Induced Breast Cancer Cell Functions

Antagonists of IGF:Vitronectin Interactions Inhibit IGF-I–Induced Breast Cancer Cell Functions

Two olfactory receptors—OR2A4/7 and OR51B5—differentially affect epidermal proliferation and differentiation

Attenuated kallikrein‐related peptidase activity disrupts desquamation and leads to stratum corneum thickening in human skin equivalent models

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