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Unusual Suspects: Bone and Cartilage ECM Proteins as Carcinoma Facilitators.

ABSTRACT: The extracellular matrix (ECM) is the complex three-dimensional network of fibrous proteins and proteoglycans that constitutes an essential part of every tissue to provide support for normal tissue homeostasis. Tissue specificity of the ECM in its topology and structure supports unique biochemical and mechanical properties of each organ. Cancers, like normal tissues, require the ECM to maintain multiple processes governing tumor development, progression and spread. A large body of experimental and clinical evidence has now accumulated to demonstrate essential roles of numerous ECM components in all cancer types. Latest findings also suggest that multiple tumor types express, and use to their advantage, atypical ECM components that are not found in the cancer tissue of origin. However, the understanding of cancer-specific expression patterns of these ECM proteins and their exact roles in selected tumor types is still sketchy. In this review, we summarize the latest data on the aberrant expression of bone and cartilage ECM proteins in epithelial cancers and their specific functions in the pathogenesis of carcinomas and discuss future directions in exploring the utility of this selective group of ECM components as future drug targets.

SUBMITTER: Sorvina A

PROVIDER: S-EPMC9913341 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Unusual Suspects: Bone and Cartilage ECM Proteins as Carcinoma Facilitators.

Sorvina Alexandra A Antoniou Michael M Esmaeili Zahra Z Kochetkova Marina M

Cancers 20230127 3

The extracellular matrix (ECM) is the complex three-dimensional network of fibrous proteins and proteoglycans that constitutes an essential part of every tissue to provide support for normal tissue homeostasis. Tissue specificity of the ECM in its topology and structure supports unique biochemical and mechanical properties of each organ. Cancers, like normal tissues, require the ECM to maintain multiple processes governing tumor development, progression and spread. A large body of experimental a ...[more]

PMID: 36765749

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Project description:Articular and growth plate cartilage both arise from condensations of mesenchymal cells, but ultimately develop important histological and functional differences. Each is composed of three layers-the superficial, mid and deep zones of articular cartilage and the resting, proliferative and hypertrophic zones of growth plate cartilage. The bone morphogenetic protein (BMP) system plays an important role in cartilage development. A gradient in expression of BMP-related genes has been observed across growth plate cartilage, likely playing a role in zonal differentiation. To investigate the presence of a similar expression gradient in articular cartilage, we used laser capture microdissection (LCM) to separate murine growth plate and articular cartilage from the proximal tibia into their six constituent zones, and used a solution hybridization assay with color-coded probes (nCounter) to quantify mRNAs for 30 different BMP-related genes in each zone. In situ hybridization and immunohistochemistry were then used to confirm spatial expression patterns. Expression gradients for Bmp2 and 6 were observed across growth plate cartilage with highest expression in hypertrophic zone. However, intracellular BMP signaling, assessed by phospho-Smad1/5/8 immunohistochemical staining, appeared to be higher in the proliferative zone and prehypertrophic area than in hypertrophic zone, possibly due to high expression of Smad7, an inhibitory Smad, in the hypertrophic zone. We also found BMP expression gradients across the articular cartilage with BMP agonists primarily expressed in the superficial zone and BMP functional antagonists primarily expressed in the deep zone. Phospho-Smad1/5/8 immunohistochemical staining showed a similar gradient. In combination with previous evidence that BMPs regulate chondrocyte proliferation and differentiation, the current findings suggest that BMP signaling gradients exist across both growth plate and articular cartilage and that these gradients may contribute to the spatial differentiation of chondrocytes in the postnatal endochondral skeleton.

Project description:BackgroundThrough a comprehensive analysis of the joint synovial fluid produced in the process of rabbit articular cartilage regeneration, the role and characteristics of knee synovial fluid in the process of decalcified bone transplantation-induced articular cartilage regeneration were explored.MethodsTwenty New Zealand white rabbits (approximately 2.5 kg in weight) were selected, and bilateral distal femoral bones from two randomly selected rabbits were extracted. After decalcification, the bones were cut into 2 mm × 4 cm long decalcified bone strips. Meanwhile, the other 18 rabbits were randomly divided into three groups: the test group (8 rabbits), the positive control group (6 rabbits), and the blank group (4 rabbits). In the test group, the decalcified bone joint was transplanted into the rabbits at the articular cartilage defect; in the positive control group, the articular cartilage defect of the rabbits were treated and put aside; in the blank group, no rabbits were treated. On the day of transplantation, and on the 4th, 8th, 12th, and 16th weeks after transplantation, the joint synovial fluid of each group was taken for two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) analysis, and related database verification and identification, and compared with the positive control group and the blank group.ResultsUsing 2D-PAGE to separate various proteins in the synovial fluid of the rabbit knee joints, it was found that there were differential protein spots in the test group compared with the blank group and the positive control group. After conducting a comparative search and query in the UniProt database, through comprehensive analysis, it was finally found that three proteins with molecular weights of 23,429.4, 57,431.4, and 26,071.1 that may be related to the regeneration of articular cartilage appeared in the test group.ConclusionsIn the process of inducing the regeneration of articular cartilage using decalcified bone transplantation, knee joint synovial fluid produced specific proteins, which may play an important role in the regeneration of articular cartilage. These findings may offer novel ideas in laying a foundation for the in-depth study of articular cartilage regeneration.

Dataset Information

Unusual Suspects: Bone and Cartilage ECM Proteins as Carcinoma Facilitators.

Publications

Unusual Suspects: Bone and Cartilage ECM Proteins as Carcinoma Facilitators.

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