-
Secreted modular calcium-binding proteins in pathophysiological processes and embryonic development.Chinese Medical Journal Oct 2019Secreted modular calcium-binding proteins (SMOCs) are extracellular glycoproteins of the secreted protein, acidic, and rich in cysteine-related modular calcium-binding... (Review)
Review
OBJECTIVE
Secreted modular calcium-binding proteins (SMOCs) are extracellular glycoproteins of the secreted protein, acidic, and rich in cysteine-related modular calcium-binding protein family and include two isoforms, SMOC1 and SMOC2, in humans. Functionally, SMOCs bind to calcium for various cell functions. In this review, we provided a summary of the most recent advancements in and findings of SMOC1 and SMOC2 in development, homeostasis, and disease states.
DATA SOURCES
All publications in the PubMed database were searched and retrieved (up to July 24, 2019) using various combinations of keywords searching, including SMOC1, SMOC2, and diseases.
STUDY SELECTION
All original studies and review articles of SMOCs in human diseases and embryo development written in English were retrieved and included.
RESULTS
SMOC1 and SMOC2 regulate embryonic development, cell homeostasis, and disease pathophysiology. They play an important role in the regulation of cell cycle progression, cell attachment to the extracellular matrix, tissue fibrosis, calcification, angiogenesis, birth defects, and cancer development.
CONCLUSIONS
SMOC1 and SMOC2 are critical regulators of many cell biological processes and potential therapeutic targets for the control of human cancers and birth defects.
Topics: Calcification, Physiologic; Calcium-Binding Proteins; Cell Adhesion; Cell Cycle; Embryonic Development; Homeostasis; Humans; Inflammation; Neoplasms; Neovascularization, Physiologic; Osteonectin; Waardenburg Syndrome
PubMed: 31613820
DOI: 10.1097/CM9.0000000000000472 -
Tissue Engineering. Part A Apr 2022Failure to regenerate the gradient tendon-bone interface of the enthesis results in poor clinical outcomes for surgical repair. The goal of this study was to evaluate...
Failure to regenerate the gradient tendon-bone interface of the enthesis results in poor clinical outcomes for surgical repair. The goal of this study was to evaluate the potential of composite cell sheets for engineering of the tendon-bone interface to improve regeneration of the functionally graded tissue. We hypothesize that stacking cell sheets at early stages of differentiation into tenogenic and osteogenic progenitors will create a composite structure with integrated layers. Cell sheets were fabricated on methyl cellulose and poly(N-isopropylacrylamide) thermally reversible polymers with human adipose-derived stem cells and differentiated into progenitors of tendon and bone with chemical induction media. Tenogenic and osteogenic cell sheets were stacked, and the engineered tendon-bone interface (TM-OM) was characterized in comparison to stacked cell sheet controls cultured in basal growth medium (GM-GM), osteogenic medium (OM-OM), and tenogenic medium (TM-TM). Samples were characterized by histology, quantitative real-time polymerase chain reaction, and immunofluorescent staining for markers of tendon, fibrocartilage, and bone including mineralization, scleraxis, tenomodulin, , , , osteonectin, and osterix. After 1 week co-culture in basal growth medium, TM-OM cell sheets formed a tissue construct with integrated layers expressing markers of tendon, mineralized fibrocartilage, and bone with a spatial gradient in RUNX2 expression. Tenogenic cell sheets had increased expression of scleraxis and tenomodulin. Osteogenic cell sheets exhibited mineralization 1 week after stacking and upregulation of osterix and osteonectin. Additionally, in the engineered interface, there was significantly increased gene expression of and , indicative of endochondral ossification. These results highlight the potential for composite cell sheets fabricated with adipose-derived stem cells for engineering of the tendon-bone interface. Impact statement This study presents a method for fabrication of the tendon-bone interface using stacked cell sheets of tenogenic and osteogenic progenitors differentiated from human adipose-derived mesenchymal stem cells, resulting in a composite structure expressing markers of tendon, mineralized fibrocartilage, and bone. This work is an important step toward regeneration of the biological gradient of the enthesis and demonstrates the potential for engineering complex tissue interfaces from a single autologous cell source to facilitate clinical translation.
Topics: Cell Differentiation; Core Binding Factor Alpha 1 Subunit; Humans; Mesenchymal Stem Cells; Osteonectin; Tendons; Tissue Engineering
PubMed: 34476994
DOI: 10.1089/ten.TEA.2021.0072 -
Oncotarget Oct 2016Secreted Protein Acidic and Rich in Cysteine (SPARC) is a matricellular glycoprotein that is implicated in myriad physiological and pathological conditions characterized... (Review)
Review
Secreted Protein Acidic and Rich in Cysteine (SPARC) is a matricellular glycoprotein that is implicated in myriad physiological and pathological conditions characterized by extensive remodeling and plasticity. The functions and disease association of SPARC in cancer is being increasingly appreciated as it plays multi-faceted contextual roles depending on the cancer type, cell of origin and the unique cancer milieu at both primary and metastatic sites. Herein we will review our current knowledge of the role of SPARC in the multistep cascades of urinary bladder carcinogenesis, progression and metastasis from preclinical models and clinical data and shine the light on its prognostic and therapeutic potentials.
Topics: Animals; Carcinogenesis; Disease Progression; Humans; Neoplasm Invasiveness; Osteonectin; Urinary Bladder Neoplasms; Urothelium
PubMed: 27564266
DOI: 10.18632/oncotarget.11590 -
Biomolecules Jul 2023The SPARC gene plays multiple roles in extracellular matrix synthesis and cell shaping, associated with tumor cell migration, invasion, and metastasis. The SPARC gene is... (Review)
Review
The SPARC gene plays multiple roles in extracellular matrix synthesis and cell shaping, associated with tumor cell migration, invasion, and metastasis. The SPARC gene is also involved in the epithelial-mesenchymal transition (EMT) process, which is a critical phenomenon leading to a more aggressive cancer cell phenotype. SPARC gene overexpression has shown to be associated with poor survival in the mesothelioma (MESO) cohort from the TCGA database, indicating that this gene may be a powerful prognostic factor in MESO. Its overexpression is correlated with the immunosuppressive tumor microenvironment. Here, we summarize the omics advances of the SPARC gene, including the summary of SPARC gene expression associated with prognosis in pancancer and MESO, the immunosuppressive microenvironment, and cancer cell stemness. In addition, SPARC might be targeted by microRNAs. Notably, despite the controversial functions on angiogenesis, SPARC may directly or indirectly contribute to tumor angiogenesis in MESO. In conclusion, SPARC is involved in tumor invasion, metastasis, immunosuppression, cancer cell stemness, and tumor angiogenesis, eventually impacting patient survival. Strategies targeting this gene may provide novel therapeutic approaches to the treatment of MESO.
Topics: Humans; Cell Line, Tumor; Mesothelioma; MicroRNAs; Mesothelioma, Malignant; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Tumor Microenvironment; Osteonectin
PubMed: 37509139
DOI: 10.3390/biom13071103 -
Journal of Ocular Pharmacology and... Sep 2015Secreted protein acidic and rich in cysteine (SPARC), also known as osteonectin or BM-40, is the prototypical matricellular protein. Matricellular proteins are... (Review)
Review
Secreted protein acidic and rich in cysteine (SPARC), also known as osteonectin or BM-40, is the prototypical matricellular protein. Matricellular proteins are nonstructural secreted proteins that provide an integration between cells and their surrounding extracellular matrix (ECM). Regulation of the ECM is important in maintaining the physiologic function of tissues. Elevated levels of SPARC have been identified in a variety of diseases involving pathologic tissue remodeling, such as hepatic fibrosis, systemic sclerosis, and certain carcinomas. Within the eye, SPARC has been identified in the trabecular meshwork, lens, and retina. Studies have begun to show the role of SPARC in these tissues and its possible role, specifically in primary open-angle glaucoma, cataracts, and proliferative vitreoretinopathy. SPARC may, therefore, be a therapeutic target in the treatment of certain ocular diseases. Further investigation into the mechanism of action of SPARC will be necessary in the development of SPARC-targeted therapy.
Topics: Animals; Cysteine; Eye; Glaucoma, Open-Angle; Humans; Lens, Crystalline; Osteonectin
PubMed: 26167673
DOI: 10.1089/jop.2015.0057 -
Journal of Bone and Mineral Research :... Apr 2005The skeleton is the main source of osteonectin mRNA in adults of the seawater teleost sea bream Sparus auratus. It is expressed by cells forming the basement membrane of...
UNLABELLED
The skeleton is the main source of osteonectin mRNA in adults of the seawater teleost sea bream Sparus auratus. It is expressed by cells forming the basement membrane of calcifying tissue indicating that, as in mammals, it may play a role in osteoblast differentiation. PTHrP induced downregulation of osteonectin mRNA in vitro in scales, a mineralizing tissue with bone-like metabolism. This indicates a means to redirect calcium to activities such as vitellogenesis when this ion is in high demand.
INTRODUCTION
Osteonectin is a unique matricellular calcium-binding glycoprotein and a major noncollagenous constituent of higher eukaryote bone. In terrestrial vertebrates, it has been associated with development, remodeling, cell turnover, and tissue repair, all processes involving substantial changes in extracellular matrix (ECM) structure. In skeleton biology, osteonectin has been described as a positive factor in the mineralization process as well as in osteoblastic cell lineage differentiation and is downregulated by the hypercalcemic hormone PTH. In this study, we report the cloning and characterization of bream S. auratus osteonectin cDNA and its tissue and cellular distribution. Its high expression by fish scales provides a unique in vitro bioassay with which to study regulation of osteonectin gene expression by the recently isolated piscine PTH-related peptide (PTHrP).
MATERIALS AND METHODS
An intervertebral tissue cDNA library from S. auratus was the source of the full-length cDNA clone for osteonectin. Expression studies were performed by semiquantitative RT-PCR, Northern blot, and in situ hybridization analysis. Moreover, an in vitro bioassay with S. auratus scales was specifically developed for measuring the effect of PTHrP on osteonectin expression.
RESULTS AND CONCLUSIONS
Phylogenetic analysis showed that S. auratus osteonectin is highly homologous with previously reported osteonectins, supporting the idea of a conserved function for this protein in the ECM. Its expression pattern in adult tissues from S. auratus was markedly biased toward skeletal structures of both dermal or endochondral origin. More specifically, the localization of the osteonectin mRNA in the basement membrane that separates the epithelia from the underlying mineralized connective tissue supports a role for this protein in calcified matrix turnover. Furthermore, the recently identified piscine hypercalcemic factor PTHrP downregulates osteonectin expression in scales, suggesting a catabolic action for this hormone on these structures.
Topics: Amino Acid Sequence; Animals; Base Sequence; DNA, Complementary; Down-Regulation; Gene Expression; Molecular Sequence Data; Osteonectin; Parathyroid Hormone-Related Protein; Phylogeny; RNA, Messenger; Sea Bream; Sequence Alignment; Tissue Distribution; Vitellogenesis
PubMed: 15765188
DOI: 10.1359/JBMR.041201 -
Microvascular Research Jan 2009Counteradhesive proteins are a group of genetically and structurally distinct multidomain proteins that have been grouped together for their ability to inhibit... (Review)
Review
Counteradhesive proteins are a group of genetically and structurally distinct multidomain proteins that have been grouped together for their ability to inhibit cell-substrate interactions. Three counteradhesive proteins that influence endothelial cell behavior include thrombospondin (TSP)1, (SPARC) (Secreted Protein Acidic and Rich in Cysteine), also known as osteonectin, and tenascin. More recently, these proteins have been shown to regulate not only cell-matrix interactions but cell-cell interactions as well. TSP1 increases tyrosine phosphorylation of components of the cell-cell adherens junctions or zonula adherens (ZA) and opens the paracellular pathway in human lung microvascular endothelia. The epidermal growth factor (EGF)-repeats of TSP1 activate the (EGF) receptor (EGFR) and ErbB2, and these two receptor protein tyrosine kinases (PTK)s participate in ZA protein tyrosine phosphorylation and barrier disruption in response to the TSP1 stimulus. For the barrier response to TSP1, EGFR/ErbB2 activation is necessary but insufficient. Protein tyrosine phosphatase (PTP)mu counter-regulates phosphorylation of selected tyrosine residues within the cytoplasmic domain of EGFR. Although tenascin, like TSP1, also contains EGF-like repeats and is known to activate EGFR, whether it also opens the paracellular pathway is unknown. In addition to TSP1, tenascin, and the other TSP family members, there are numerous other proteins that also contain EGF-like repeats and participate in hemostasis, wound healing, and tissue remodeling. EGFR not only responds to direct binding of EGF motif-containing ligands but can also be transactivated by a wide range of diverse stimuli. In fact, several established mediators of increased vascular permeability and/or lung injury, including thrombin, tumor necrosis factor-alpha, platelet-activating factor, bradykinin, angiopoietin, and H(2)O(2), transactivate EGFR. It is conceivable that EGFR serves a pivotal signaling role in a final common pathway for the pulmonary response to selected injurious stimuli. SPARC/Osteonectin also increases tyrosine phosphorylation of ZA proteins and opens the endothelial paracellular pathway in a PTK-dependent manner. The expression of the counteradhesive proteins is increased in response to a wide range of injurious stimuli. It is likely that these same molecules participate in the host response to acute lung injury and are operative during the barrier response within the pulmonary microvasculature.
Topics: Animals; Capillary Permeability; Endothelium, Vascular; Humans; Lung; Osteonectin; Phosphotyrosine; Receptor, ErbB-2; Signal Transduction; Thrombospondin 1
PubMed: 18952113
DOI: 10.1016/j.mvr.2008.08.008 -
Cancer Treatment Reviews Nov 2011SPARC (a secreted protein acidic and rich in cysteine) has a reputation for being potent anti-cancer and anti-obesity molecule. It is one of the first known... (Review)
Review
SPARC (a secreted protein acidic and rich in cysteine) has a reputation for being potent anti-cancer and anti-obesity molecule. It is one of the first known matricellular protein that modulates interactions between cells and extracellular matrix (ECM) and is associated with the 'balance' of white adipose tissue (WAT) as well as lipogenesis and lipolysis during adipogenesis. Adipogenesis is an indication for the development of obesity and has been related to a wide variety of cancers including breast cancer, endometrial cancer, esophageal cancer, etc. Adipogenesis mainly involves ECM remodeling, changes in cell-ECM interactions, and cytoskeletal rearrangement. SPARC can also prevent hypertrophy of adipocytes and hyperplasia of adipocyte progenitors. In addition to SPARC's inhibitory role in adipogenesis, it has also been known to be involved in cell cycle, cell proliferation, cell invasion, adhesion, migration, angiogenesis and apoptosis. Molecular cancer biology and clinical biochemistry have significantly enhanced our understanding of the mechanisms that motivate the anti-cancer and anti-obesity action of SPARC. Recent studies elucidating the signaling pathways that are activated by SPARC can help develop the beneficial aspects of SPARC for cancer therapy and obesity prevention. This review focuses on the anti-cancer role of SPARC as it pertains to obesity.
Topics: Adipogenesis; Animals; Anti-Obesity Agents; Antineoplastic Agents; Humans; Neoplasms; Obesity; Osteonectin
PubMed: 21237573
DOI: 10.1016/j.ctrv.2010.12.001 -
Immunity Sep 2022Caloric restriction (CR) reduces inflammation and the incidence of chronic diseases, thereby extending healthspan and lifespan. In this issue of Immunity, Ryu et al....
Caloric restriction (CR) reduces inflammation and the incidence of chronic diseases, thereby extending healthspan and lifespan. In this issue of Immunity, Ryu et al. (2022) propose that reduction of SPARC, a matricellular protein, during CR offers beneficial effects by reducing SPARC-driven inflammatory phenotypes in macrophages.
Topics: Caloric Restriction; Humans; Inflammation; Longevity; Osteonectin
PubMed: 36103855
DOI: 10.1016/j.immuni.2022.08.012 -
World Journal of Gastroenterology Oct 2014Pancreatic cancer has a considerably poor prognosis with a 5-year survival probability of less than 5% when all stages are combined. Pancreatic cancer is characterized... (Review)
Review
Pancreatic cancer has a considerably poor prognosis with a 5-year survival probability of less than 5% when all stages are combined. Pancreatic cancer is characterized by its dense stroma, which is involved in the critical interplay with the tumor cells throughout tumor progression and furthermore, creates a barrier restricting efficient penetration of therapeutics. Alterations in a large number of genes are reflected by a limited number of signaling pathways, which are potential targets. Understanding more about the molecular basis of this devastating cancer type regarding tumor microenvironment, distinct subpopulations of cells, epithelial-to-mesenchymal transition and inflammation will lead to the development of various targeted therapies for controlling tumor growth and metastasis. In this complex scenario of pancreatic cancer, especially members of the "small integrin binding ligand N-linked glycoproteins" (SIBLINGs) and "secreted protein acidic and rich in cysteine" (SPARC) families have emerged due to their prominent roles in properties including proliferation, differentiation, apoptosis, adhesion, migration, angiogenesis, wound repair and regulation of extracellular matrix remodeling. SIBLINGs consist of five members, which include osteopontin (OPN), bone sialoprotein, dentin matrix protein 1, dentin sialophosphoprotein and matrix extracellular phosphoglycoprotein. The SPARC family of modular extracellular proteins is comprised of SPARC/osteonectin (ON) and SPARC-like 1 (hevin); secreted modular calcium binding proteins; testicans and follistatin-like protein. In this review, we especially focus on OPN and ON, elaborating on their special and growing importance in pancreatic cancer diagnosis and prognosis.
Topics: Animals; Biomarkers, Tumor; Disease Progression; Humans; Osteonectin; Osteopontin; Pancreatic Neoplasms; Prognosis; Signal Transduction; Tumor Microenvironment
PubMed: 25356037
DOI: 10.3748/wjg.v20.i40.14747