A Marine Collagen-Based Biomimetic Hydrogel Recapitulates Cancer Stem Cell Niche and Enhances Progression and Chemoresistance in Human Ovarian Cancer.

Recent attention has focused on the development of an effective three-dimensional (3D) cell culture system enabling the rapid enrichment of cancer stem cells (CSCs) that are resistant to therapies and serving as a useful in vitro tumor model that accurately reflects in vivo behaviors of cancer cells. Presently, an effective 3D in vitro model of ovarian cancer (OC) was developed using a marine collagen-based hydrogel. Advantages of the model include simplicity, efficiency, bioactivity, and low cost. Remarkably, OC cells grown in this hydrogel exhibited biochemical and physiological features, including (1) enhanced cell proliferation, migration and invasion, colony formation, and chemoresistance; (2) suppressed apoptosis with altered expression levels of apoptosis-regulating molecules; (3) upregulated expression of crucial multidrug resistance-related genes; (4) accentuated expression of key molecules associated with malignant progression, such as epithelial-mesenchymal transition transcription factors, Notch, and pluripotency biomarkers; and (5) robust enrichment of ovarian CSCs. The findings indicate the potential of our 3D in vitro OC model as an in vitro research platform to study OC and ovarian CSC biology and to screen novel therapies targeting OC and ovarian CSCs.

Marine Collagen as A Promising Biomaterial for Biomedical Applications.

This review focuses on the expanding role of marine collagen (MC)-based scaffolds for biomedical applications. A scaffold-a three-dimensional (3D) structure fabricated from biomaterials-is a key supporting element for cell attachment, growth, and maintenance in 3D cell culture and tissue engineering. The mechanical and biological properties of the scaffolds influence cell morphology, behavior, and function. MC, collagen derived from marine organisms, offers advantages over mammalian collagen due to its biocompatibility, biodegradability, easy extractability, water solubility, safety, low immunogenicity, and low production costs. In recent years, the use of MC as an increasingly valuable scaffold biomaterial has drawn considerable attention from biomedical researchers. The characteristics, isolation, physical, and biochemical properties of MC are discussed as an understanding of MC in optimizing the subsequent modification and the chemistries behind important tissue engineering applications. The latest technologies behind scaffold processing are assessed and the biomedical applications of MC and MC-based scaffolds, including tissue engineering and regeneration, wound dressing, drug delivery, and therapeutic approach for diseases, especially those associated with metabolic disturbances such as obesity and diabetes, are discussed. Despite all the challenges, MC holds great promise as a biomaterial for developing medical products and therapeutics.

Descriptive and functional characterization of epidermal growth factor­like domain 8 in mouse cortical thymic epithelial cells by integrated analysis of gene expression signatures and networks.

Epidermal growth factor­like domain 8 (EGFL8), a newly identified member of the EGFL family, and plays negative regulatory roles in mouse thymic epithelial cells (TECs) and thymocytes. However, the role of EGFL8 in these cells remains poorly understood. In the present study, in order to characterize the function of EGFL8, genome­wide expression profiles in EGFL8­overexpressing or ­silenced mouse cortical TECs (cTECs) were analyzed. Microarray analysis revealed that 458 genes exhibited a >2­fold change in expression levels in the EGFL8­overexpressing vs. the EGFL8­silenced cTECs. Several genes involved in a number of cellular processes, such as the cell cycle, proliferation, growth, migration and differentiation, as well as in apoptosis, reactive oxygen species generation, chemotaxis and immune responses, were differentially expressed in the EGFL8­overexpressing or ­silenced cTECs. WST­1 analysis revealed that that the overexpression of EGFL8 inhibited cTEC proliferation. To investigate the underlying mechanisms of EGFL8 in the regulation of cTEC function, genes related to essential cellular functions were selected. Reverse transcription­polymerase chain reaction analysis revealed that EGFL8 knockdown upregulated the expression of cluster differentiation 74 (CD74), Fas ligand (FasL), C­X­C motif chemokine ligand 5 (CXCL5), CXCL10, CXCL16, C­C motif chemokine ligand 20 (CCL20), vascular endothelial growth factor­A (VEGF­A), interferon regulatory factor 7 (Irf7), insulin­like growth factor binding protein­4 (IGFBP­4), thrombospondin 1 (Thbs1) and nuclear factor κB subunit 2 (NF­κB2) genes, and downregulated the expression of angiopoietin­like 1 (Angptl1), and neuropilin­1 (Nrp1) genes. Additionally, EGFL8 silencing enhanced the expression of anti­apoptotic molecules, such as B­cell lymphoma­2 (Bcl­2) and Bcl­extra large (Bcl­xL), and that of cell cycle­regulating molecules, such as cyclin­dependent kinase 1 (CDK1), CDK4, CDK6 and cyclin D1. Moreover, gene network analysis revealed that EGFL8 exerted negative effects on VEGF­A gene expression. Hence, the altered expression of several genes associated with EGFL8 expression in cTECs highlights the important physiological processes in which EGFL8 is involved, and provides insight into its biological functions.