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Understanding the tumor microenvironment (TME) and extracellular matrix (ECM) is crucial in cancer research due to their impact on tumor progression. Collagens, major ECM components, regulate cell signaling and behavior. Of the 28 reported collagens, type XII collagen is known to be vital for ECM organization. Over-produced by cancer-associated fibroblasts (CAFs), its upregulation correlates with poor survival in various cancers. This study aimed to develop an ELISA for quantifying circulating type XII collagen as a cancer biomarker. A specific ELISA targeting the C-terminal of type XII collagen was developed and used to analyze serum samples from cancer patients (n = 203) and healthy controls (n = 33). Additionally, type XII collagen expression was assessed in CAFs and normal fibroblasts (NFs) from different tissues, both under TGF-β stimulated and non-stimulated conditions. The nordicPRO-C12 ELISA demonstrated robustness and specificity for type XII collagen. PRO-C12 levels were significantly elevated in patients with various cancers compared to healthy controls and effectively distinguished between cancer patients and controls. Findings were validated using gene expression data. Furthermore, Western blot analysis revealed increased type XII collagen expression in both CAFs and NFs upon TGF-β1 stimulation, suggesting a potential role of TGF-β1 in modulating the expression of type XII collagen in cancerous and normal tissue microenvironments. This study unveils a promising avenue for harnessing PRO-C12 as a non-invasive serum biomarker, enabling the quantification of type XII collagen fragments in cancer patients. Further investigations are warranted to explore the potential of PRO-C12 across different cancer types and disease stages, shedding light on its multifaceted role in cancer development. [ABSTRACT FROM AUTHOR]

Abstract The extracellular matrix (ECM) is reported to be involved in tumorigenesis and progression. Collagen IIX is a major ECM protein. Abnormal COL12A1 expression is associated with carcinogenesis of colorectal cancer (CRC), but its clinical value and function have not yet been analyzed. Expression, methylation, and survival were analyzed by using Oncomine, UNCLA, and GEPIA, while COL12A1 alterations and related functional networks were identified using cBioPortal. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathways（KEGG）of COL12A1 in CRC were explored using LinkOmics. Gene set enrichment analysis (GSEA) examined target networks of kinases, miRNAs, and transcription factors. We found that COL12A1 was overexpressed in CRC and the COL12A1 gene was often amplified in CRC. Survival analysis revealed that patients with higher COL12A1 expression had a poor prognosis. Expression of COL12A1 was linked to functional networks via regulating pathways involving focal adhesion, PI3K‐Akt signaling pathway, and ECM‐receptor interaction. Functional network analysis suggested that COL12A1 regulated integrin binding, collage binding, and extracellular matrix structural constituent via pathways involving some several cancer‐related kinases, miRNAs, and transcription factor. Furthermore, other FACITs genes (COL1A2, COL3A1, COL5A1, COL5A2, and COL6A3) for ECM in correlation with COL12A1 were identified to be related with the prognosis in CRC. These results suggested that the distinct fibril‐associated collagens with interrupted triple helices (FACITs) genes may serve as prognostic and therapeutic biomarkers of CRC in the future.

The extracellular matrix (ECM) is reported to be involved in tumorigenesis and progression. Collagen IIX is a major ECM protein. Abnormal COL12A1 expression is associated with carcinogenesis of colorectal cancer (CRC), but its clinical value and function have not yet been analyzed. Expression, methylation, and survival were analyzed by using Oncomine, UNCLA, and GEPIA, while COL12A1 alterations and related functional networks were identified using cBioPortal. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathways（KEGG）of COL12A1 in CRC were explored using LinkOmics. Gene set enrichment analysis (GSEA) examined target networks of kinases, miRNAs, and transcription factors. We found that COL12A1 was overexpressed in CRC and the COL12A1 gene was often amplified in CRC. Survival analysis revealed that patients with higher COL12A1 expression had a poor prognosis. Expression of COL12A1 was linked to functional networks via regulating pathways involving focal adhesion, PI3K‐Akt signaling pathway, and ECM‐receptor interaction. Functional network analysis suggested that COL12A1 regulated integrin binding, collage binding, and extracellular matrix structural constituent via pathways involving some several cancer‐related kinases, miRNAs, and transcription factor. Furthermore, other FACITs genes (COL1A2, COL3A1, COL5A1, COL5A2, and COL6A3) for ECM in correlation with COL12A1 were identified to be related with the prognosis in CRC. These results suggested that the distinct fibril‐associated collagens with interrupted triple helices (FACITs) genes may serve as prognostic and therapeutic biomarkers of CRC in the future. [ABSTRACT FROM AUTHOR]

Development of mammalian teeth and surrounding tissues includes time–space changes in the extracellular matrix composition and organization. This requires complex control mechanisms to regulate its synthesis and remodeling. Fibril-associated collagens with interrupted triple helices (FACITs) and a group of small leucine-rich proteoglycans (SLRPs) are involved in the regulation of collagen fibrillogenesis. Recently, collagen type XII and collagen type XIV, members of the FACITs family, were found in the peridental mesenchyme contributing to alveolar bone formation. This study was designed to follow temporospatial expression of collagen types XIIa and XIVa in mouse first molar and adjacent tissues from embryonic day 13, when the alveolar bone becomes morphologically apparent around the molar tooth bud, until postnatal day 22, as the posteruption stage. The patterns of decorin, biglycan, and fibromodulin, all members of the SLRPs family and interacting with collagens XIIa and XIVa, were investigated simultaneously. The situation in the tooth was related to what happens in the alveolar bone, and both were compared to the periodontal ligament. The investigation provided a complex localization of the five antigens in soft tissues, the dental pulp, and periodontal ligaments; in the mineralized tissues, predentin/dentin and alveolar bone; and junction between soft and hard tissues. The results illustrated developmentally regulated and tissue-specific changes in the balance of the two FACITs and three SLRPs.

Development of mammalian teeth and surrounding tissues includes time-space changes in the extracellular matrix composition and organization. This requires complex control mechanisms to regulate its synthesis and remodeling. Fibril-associated collagens with interrupted triple helices (FACITs) and a group of small leucine-rich proteoglycans (SLRPs) are involved in the regulation of collagen fibrillogenesis. Recently, collagen type XII and collagen type XIV, members of the FACITs family, were found in the peridentalmesenchyme contributing to alveolar bone formation. This study was designed to follow temporospatial expression of collagen types XIIa and XIVa in mouse first molar and adjacent tissues from embryonic day 13, when the alveolar bone becomes morphologically apparent around the molar tooth bud, until postnatal day 22, as the posteruption stage. The patterns of decorin, biglycan, and fibromodulin, all members of the SLRPs family and interacting with collagens XIIa and XIVa, were investigated simultaneously. The situation in the tooth was related to what happens in the alveolar bone, and both were compared to the periodontal ligament. The investigation provided a complex localization of the five antigens in soft tissues, the dental pulp, and periodontal ligaments; in the mineralized tissues, predentin/dentin and alveolar bone; and junction between soft and hard tissues. The results illustrated developmentally regulated and tissue-specific changes in the balance of the two FACITs and three SLRPs. [ABSTRACT FROM AUTHOR]

Snake venom metalloproteinases (SVMPs) affect the extracellular matrix (ECM) in multiple and complex ways. Previously, the combination of various methodological platforms, including electron microscopy, histochemistry, immunohistochemistry, and Western blot, has allowed a partial understanding of such complex pathology. In recent years, the proteomics analysis of exudates collected in the vicinity of tissues affected by SVMPs has provided novel and exciting information on SVMP-induced ECM alterations. The presence of fragments of an array of ECM proteins, including those of the basement membrane, has revealed a complex pathological scenario caused by the direct action of SVMPs. In addition, the time-course analysis of these changes has underscored that degradation of some fibrillar collagens is likely to depend on the action of endogenous proteinases, such as matrix metalloproteinases (MMPs), synthesized as a consequence of the inflammatory process. The action of SVMPs on the ECM also results in the release of ECM-derived biologically-active peptides that exert diverse actions in the tissue, some of which might be associated with reparative events or with further tissue damage. The study of the effects of SVMP on the ECM is an open field of research which may bring a renewed understanding of snake venom-induced pathology. [ABSTRACT FROM AUTHOR]

Snake venom metalloproteinases (SVMPs) affect the extracellular matrix (ECM) in multiple and complex ways. Previously, the combination of various methodological platforms, including electron microscopy, histochemistry, immunohistochemistry, and Western blot, has allowed a partial understanding of such complex pathology. In recent years, the proteomics analysis of exudates collected in the vicinity of tissues affected by SVMPs has provided novel and exciting information on SVMP-induced ECM alterations. The presence of fragments of an array of ECM proteins, including those of the basement membrane, has revealed a complex pathological scenario caused by the direct action of SVMPs. In addition, the time-course analysis of these changes has underscored that degradation of some fibrillar collagens is likely to depend on the action of endogenous proteinases, such as matrix metalloproteinases (MMPs), synthesized as a consequence of the inflammatory process. The action of SVMPs on the ECM also results in the release of ECM-derived biologically-active peptides that exert diverse actions in the tissue, some of which might be associated with reparative events or with further tissue damage. The study of the effects of SVMP on the ECM is an open field of research which may bring a renewed understanding of snake venom-induced pathology.

The collagens represent a family of trimeric extracellular matrix molecules used by cells for structural integrity and other functions. The three α chains that form the triple helical part of the molecule are composed of repeating peptide triplets of glycine-X-Y. X and Y can be any amino acid but are often proline and hydroxyproline, respectively. Flanking the triple helical regions (i.e., Col domains) are non-glycine-X-Y regions, termed non-collagenous domains. These frequently contain recognizable peptide modules found in other matrix molecules. Proper tissue function depends on correctly assembled molecular aggregates being incorporated into the matrix. This review highlights some of the structural characteristics of collagen types I-XXVIII. [ABSTRACT FROM AUTHOR]