Dermatopathologic features of cutaneous squamous cell carcinoma and actinic keratosis: Consensus criteria and proposed reporting guidelines.

Background: There is considerable variation in the literature regarding the dermatopathologic diagnostic features of and reporting guidelines for actinic keratosis (AK) and cutaneous squamous cell carcinoma (cSCC).

Objective: To develop consensus recommendations regarding diagnostic criteria, nomenclature, and reporting of AK and cSCC.

Methods: Literature review and cross-sectional multiround Delphi process including an international group of expert dermatopathologists followed by a consensus meeting.

Emerging roles for ectodomain shedding in the regulation of inflammatory responses.

The multistep model of leukocyte recruitment to sites of inflammation has helped elucidate specific molecular cues for each of the individual steps. However, it is less clear how cells transition between the different steps and how the complex interactions are coordinately regulated. Once a leukocyte sticks to the endothelium, it only takes a few minutes to reach the subendothelial basement membrane, so the transitions and regulatory mechanisms must be rapid.

ADAM10 mediates ectodomain shedding of the betacellulin precursor activated by p-aminophenylmercuric acetate and extracellular calcium influx.

Betacellulin belongs to the family of epidermal growth factor-like growth factors that are expressed as transmembrane precursors and undergo proteolytic ectodomain shedding to release a soluble mature growth factor. In this study, we investigated the ectodomain shedding of the betacellulin precursor (pro-BTC) in conditionally immortalized wild-type (WT) and ADAM-deficient cell lines. Sequential ectodomain cleavage of the predominant cell-surface 40-kDa form of pro-BTC generated a major (26-28 kDa) and two minor (20 and 15 kDa) soluble forms and a cellular remnant lacking the ectodomain (12 kDa).

A disintegrin and metalloproteinase 10-mediated cleavage and shedding regulates the cell surface expression of CXC chemokine ligand 16.

CXC chemokine ligand (CXCL)16 and scavenger receptor for phosphatidylserine and oxidized low-density lipoprotein were independently identified as a chemokine and a scavenger receptor, respectively, but have since been shown to be identical. CXCL16 is synthesized as a transmembrane protein with its chemokine domain at the end of a mucin-rich stalk. When expressed at the cell surface, CXCL16 functions as a scavenger receptor, binding and internalizing oxidized low-density lipoprotein and bacteria.

Stimulated shedding of vascular cell adhesion molecule 1 (VCAM-1) is mediated by tumor necrosis factor-alpha-converting enzyme (ADAM 17).

A variety of cell surface adhesion molecules can exist as both transmembrane proteins and soluble circulating forms. Increases in the levels of soluble adhesion molecules have been correlated with a variety of inflammatory diseases, suggesting a pathological role. Although soluble forms are thought to result from proteolytic cleavage from the cell surface, relatively little is known about the proteases responsible for their release.

An NF-kappaB-dependent transcriptional program is required for collagen remodeling by human smooth muscle cells.

Although remodeling of vessels can dramatically alter lumen diameter and clinical sequelae, the molecular mechanisms regulating extracellular matrix turnover and remodeling are still not well understood. To investigate these processes in human smooth muscle, we have compared their culture on monomer and polymerized collagen gels, conditions that mimic some of the features of injured and normal vessels, respectively. We show that culture on polymerized, but not monomer, collagen leads to the activation of the transcription factor NF-kappaB through phosphorylation and degradation of its inhibitor, IkappaBalpha.

Efficient expression of exogenous genes in primary vascular cells using IRES-based retroviral vectors.

Analysis of gene function in primary vascular cells has been particularly limited by low transfection efficiencies. Using internal ribosomal entry site (IRES)-based retroviral vectors, we demonstrate efficient infection (range of 45%-95%) of primary human endothelial and smooth muscle cells with genes varying in size from 1.3 to 4.