• bioinformatics
• keratinocyte cancer
• lipidomics
• mass spectrometry imaging
• metabolomics

• Carcinoma, Basal Cell/diagnosis
• Carcinoma, Basal Cell/metabolism
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods
• Machine Learning
• Skin Neoplasms/diagnosis
• Skin Neoplasms/metabolism
• Animals
• Mice
• Metabolomics/methods
• Sensitivity and Specificity
• Algorithms
• Biomarkers, Tumor/metabolism
• Humans

• metastasis
• neoplasm metastasis
• oral squamous cell carcinoma
• systematic review

• cell differentiation
• cellular reprograming
• epithelial cell
• extracellular matrix
• laminin
• ocular surface
• transdifferentiation

• extracellular matrix
• fibrosis
• glomerulus
• proteomics
• single-cell RNA sequencing
• tubulointerstitium

• Cancer
• Hemidesmosome
• Integrin
• Laminin
• Organoid
• Pancreas

• Animals
• Carcinoma, Pancreatic Ductal/genetics
• Carcinoma, Pancreatic Ductal/metabolism
• Cell Proliferation
• Hemidesmosomes/metabolism
• Humans
• Integrin alpha6beta4/genetics
• Laminin/metabolism
• Mice
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/metabolism
• Proteomics
• Proto-Oncogene Proteins p21(ras)/genetics
• Proto-Oncogene Proteins p21(ras)/metabolism

• A25236 Cancer Research UK
• Biotechnology and Biological Sciences Research Council
• MR/L011840/1 Medical Research Council
• 19258 Cancer Research UK
• C13329/A21671 Cancer Research UK
• 21671 Cancer Research UK
• 203128/Z/16/Z Wellcome Trust
• A19258 Cancer Research UK

• adhesome
• anticancer drug sensitivity
• hemidesmosome
• integrin alpha 6 beta 4
• integrin alpha v beta 3
• integrin crosstalk
• keratins 5/14
• laminin-332

• 21671 Cancer Research UK
• Hrvatska Zaklada za Znanost
• Cancer Research UK
• European Cooperation in Science and Technology

• cell culture
• cell therapy
• cornea
• endothelial cells
• extracellular matrix
• proteins

Oral squamous cell carcinoma (OSCC) is a common malignant tumor worldwide. Metastasis is the main cause of the death of OSCC patients. Long noncoding RNAs (lncRNAs), one of the key factors affecting OSCC metastasis, are a subtype of RNA with a length of more than 200 nucleotides that has little or no coding potential. In recent years, the important role played by lncRNAs in biological processes, such as chromatin modification, transcription regulation, RNA stability regulation, and mRNA translation, has been gradually revealed. More and more studies have shown that lncRNAs can regulate the metastasis of various tumors including OSCC at epigenetic, transcriptional, and post-transcriptional levels. In this review, we mainly discussed the role and possible mechanisms of lncRNAs in OSCC metastasis. Most lncRNAs act as oncogenes and only a few lncRNAs have been shown to inhibit OSCC metastasis. Besides, we briefly introduced the research status of cancer-associated fibroblasts-related lncRNAs in OSCC metastasis. Finally, we discussed the research prospects of lncRNAs-mediated crosstalk between OSCC cells and the tumor microenvironment in OSCC metastasis, especially the potential research value of exosomes and lymphangiogenesis. In general, lncRNAs are expected to be used for screening, treatment, and prognosis monitoring of OSCC metastasis, but more work is still required to better understand the biological function of lncRNAs.

• cancer-associated fibroblasts
• exosomes
• lncRNAs
• metastasis
• oral squamous cell carcinoma
• tumor microenvironment

To determine the composition of extracellular matrix (ECM) proteins secreted by a conjunctival epithelial cell line and to identify components that aid conjunctival epithelial cell culture.

Human conjunctival epithelial cell line (HCjE-Gi) cells were cultured in serum-free media and their ECM isolated using ammonium hydroxide. Growth characteristics were evaluated for fresh HCjE-Gi cells plated onto ECMs obtained from 3- to 28-day cell cultures. Mass spectrometry was used to characterize the ECM composition over 42 culture days. Cell adhesion and growth on pre-adsorbed fibronectin and α-2-HS-glycoprotein (α-2-HS-GP) were investigated.

Day 3 ECM provided the best substrate for cell growth compared to ECM obtained from 5- to 28-day cell cultures. Mass spectrometry identified a predominantly laminin 332 matrix throughout the time course, with progressive changes to matrix composition over time: proportional decreases in matrix-bound growth factors and increases in proteases. Fibronectin and α-2-HS-GP were 5- and 200-fold enriched as a proportion of the early ECM relative to the late ECM, respectively. Experiments on these proteins in isolation demonstrated that fibronectin supported rapid cell adhesion, whereas fibronectin and α-2-HS-GP both supported enhanced cell growth compared to tissue culture polystyrene.

These data reveal α-2-HS-GP as a candidate protein to enhance the growth of conjunctival epithelial cells and raise the possibility of exploiting these findings for targeted improvement to synthetic tissue engineered conjunctival substrates.

• age spots
• chemical synthesis
• computer modelling
• hydroxystearic acid
• pores
• skin physiology/structure

• Adult
• Aged
• Collagen Type I/metabolism
• Collagen Type III/metabolism
• Double-Blind Method
• Face
• Female
• Humans
• Mass Spectrometry
• Matrix Metalloproteinase 1/metabolism
• Middle Aged
• PPAR alpha/agonists
• Pigmentation/drug effects
• Proteomics
• Skin/drug effects
• Skin/enzymology
• Skin/metabolism
• Skin/radiation effects
• Skin Aging/drug effects
• Stearic Acids/pharmacology
• Tumor Suppressor Protein p53/metabolism
• Ultraviolet Rays

• Animals
• Cell Adhesion Molecules/pharmacology
• Cell Line
• Cell Proliferation/drug effects
• Cell Survival/drug effects
• Cell-Free System
• Clone Cells
• Extracellular Matrix/drug effects
• Extracellular Matrix/metabolism
• Humans
• Melanocytes/cytology
• Melanocytes/drug effects
• Melanocytes/metabolism
• Mice
• Rats
• Kalinin

• P30 CA016359 NCI NIH HHS
• P50 CA121974 NCI NIH HHS
• CA121974 NCI NIH HHS
• P30CA016359 NCI NIH HHS

Loss of collagen VII causes recessive dystrophic epidermolysis bullosa. Quantitative proteomics analysis of the extracellular matrix and secretome of human fibroblasts derived from pathologically altered skin reveals a global remodelling of the cellular microenvironment.

A global analysis of the microenvironment of human skin fibroblasts was carried out to reveal disease-related alterations in the extracellular proteome.

The mammalian cellular microenvironment is shaped by soluble factors and structural components, the extracellular matrix, providing physical support, regulating adhesion and signalling. A global, quantitative mass spectrometry strategy, combined with bioinformatics data processing, was developed to assess proteome differences in the microenvironment of primary human fibroblasts. We studied secreted proteins of fibroblasts from normal and pathologically altered skin and their post-translational modifications. The influence of collagen VII, an important structural component, which is lost in genetic skin fragility, was used as model. Loss of collagen VII had a global impact on the cellular microenvironment and was associated with proteome alterations highly relevant for disease pathogenesis including decrease in basement membrane components, increase in dermal matrix proteins, TGF-β and metalloproteases, but not higher protease activity. The definition of the proteome of fibroblast microenvironment and its plasticity in health and disease identified novel disease mechanisms and potential targets of intervention.

• cell adhesion
• extracellular matrix
• mass spectrometry
• proteomics

Plakoglobin (PG) is an armadillo protein that associates with both classic and desmosomal cadherins, but is primarily concentrated in mature desmosomes in epithelia. While reduced levels of PG have been reported in localized and hormone refractory prostate tumors, the functional significance of these changes is unknown. Here we report that PG expression is reduced in samples of a prostate tumor tissue array and inversely correlated with advancing tumor potential in 7 PCa cell lines. Ectopically expressed PG enhanced intercellular adhesive strength, and attenuated the motility and invasion of aggressive cell lines, whereas silencing PG in less tumorigenic cells had the opposite effect. PG also regulated cell-substrate adhesion and motility through extracellular matrix (ECM)-dependent inhibition of Src kinase, suggesting that PG’s effects were not due solely to increased intercellular adhesion. PG silencing resulted in elevated levels of the ECM protein vitronectin (VN), and exposing PG-expressing cells to VN induced Src activity. Furthermore, increased VN levels and Src activation correlated with diminished expression of PG in patient tissues. Thus, PG may inhibit Src by keeping VN low. Our results suggest that loss of intercellular adhesion due to reduced PG expression might be exacerbated by activation of Src through a PG-dependent mechanism. Furthermore, PG down-regulation during PCa progression could contribute to the known VN-dependent promotion of PCa invasion and metastasis, demonstrating a novel functional interaction between desmosomal cell-cell adhesion and cell-substrate adhesion signaling axes in prostate cancer.

Activation of hepatic stellate cells (HSCs) and subsequent uncontrolled accumulation of altered extracellular matrix (ECM) underpin liver fibrosis, a wound healing response to chronic injury, which can lead to organ failure and death. We sought to catalogue the components of fibrotic liver ECM to obtain insights into disease etiology and aid identification of new biomarkers. Cell-derived ECM was isolated from the HSC line LX-2, an in vitro model of liver fibrosis, and compared to ECM from human foreskin fibroblasts (HFFs) as a control. Mass spectrometry analyses of cell-derived ECMs identified, with ≥99% confidence, 61 structural ECM or secreted proteins (48 and 31 proteins for LX-2 and HFF, respectively). Gene ontology enrichment analysis confirmed the enrichment of ECM proteins, and hierarchical clustering coupled with protein–protein interaction network analysis revealed a subset of proteins enriched to fibrotic ECM, highlighting the existence of cell type-specific ECM niches. Thirty-six proteins were enriched to LX-2 ECM as compared to HFF ECM, of which Wnt-5a and CYR61 were validated by immunohistochemistry in human and murine fibrotic liver tissue. Future studies will determine if these and other components may play a role in the etiology of hepatic fibrosis, serve as novel disease biomarkers, or open up new avenues for drug discovery.

• Animals
• Cell Adhesion Molecules/analysis
• Cell Adhesion Molecules/physiology
• Cell Line
• Cell Movement
• Fibronectins/physiology
• Humans
• Integrin alpha3/physiology
• Keratinocytes/physiology
• Mice
• Mice, Inbred C57BL
• Kalinin

• P30 AR057216 NIAMS NIH HHS
• 5P30AR057216-02 NIAMS NIH HHS
• K99 AR060242 NIAMS NIH HHS
• P30 CA060553 NCI NIH HHS
• R01 AR041836 NIAMS NIH HHS
• R01 AR054184 NIAMS NIH HHS
• R01 AR054184-20 NIAMS NIH HHS
• CA060553 NCI NIH HHS

Cytogenetic analysis of head and neck squamous cell carcinoma (HNSCC) established several biomarkers that have been correlated to clinical parameters during the past years. Adequate cell culture model systems are required for functional studies investigating those potential prognostic markers in HNSCC. We have used a cell line, CAL 33, for the establishment of a cell culture model in order to perform functional analyses of interesting candidate genes and proteins. The cell line was cytogenetically characterized using array CGH, spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH). As a starting point for the investigation of genetic markers predicting radiosensitivity in tumor cells, irradiation experiments were carried out and radiation responses of CAL 33 have been determined. Radiosensitivity of CAL 33 cells was intermediate when compared to published data on tumor cell lines.