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Pathology Oncology Research : POR 2000Production of SPARC/osteonectin/BM-40 was determined in mouse B16 melanoma clones BL6 and F10 (high metastatic) and F1 (low metastatic). SPARC was produced greater... (Comparative Study)
Comparative Study
Production of SPARC/osteonectin/BM-40 was determined in mouse B16 melanoma clones BL6 and F10 (high metastatic) and F1 (low metastatic). SPARC was produced greater amount in BL6 and F10 than in F1 cells, showing a good agreement with their metastatic potentials. Moreover, SPARC production was not influenced by culture pH, even in the acidic conditions (= pH 5.9). Although tumor tissues show often low pH due to excessive amount of acidic metabolites such as lactate, most studies have been done in neutral pH. High SPARC production in the acidic medium, therefore, is thought to be an important potential for tumor invasive behaviour.
Topics: Animals; Clone Cells; Culture Media; Gene Expression Regulation, Neoplastic; Hydrogen-Ion Concentration; Melanoma, Experimental; Mice; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins; Osteonectin; Tumor Cells, Cultured
PubMed: 10749584
DOI: 10.1007/BF03032654 -
Archives of Toxicology 1995Osteonectin gene expression in relation to metallothionein mRNA expression was investigated in various tissues from Cd-treated rats. After a single 50 micromol/kg...
Osteonectin gene expression in relation to metallothionein mRNA expression was investigated in various tissues from Cd-treated rats. After a single 50 micromol/kg subcutaneous injection of CdCl2, Cd predominantly accumulated in the liver and metallothionein gene expression significantly increased concomitantly with Cd accumulation, but no alteration of osteonectin gene expression was observed. In the kidney and lung, both metallothionein and osteonectin mRNA increased significantly but the elevation of metallothionein mRNA levels (1 h after Cd administration) preceded that of osteonectin (3 h after administration). A significant elevation of osteonectin mRNA levels was also observed in the testis after 3 h, but that of metallothionein mRNA occurred after 6 h. Not only accumulation of Cd but also increments in both osteonectin and metallothionein mRNA were minimal in the brain, but a significant increase in gene expression was observed after 1 h for osteonectin and after 3 h for metallothionein. Since, except in the testis, metallothionein gene expression preceded osteonectin gene expression, the induced metallothionein might transpose Cd and thereby affect its levels immediately, thus reducing the levels of Cd available for accumulation in other tissues. Hence, the osteonectin-Cd interaction might be secondary to the metallothionein-Cd interaction. However, the fact that osteonectin mRNA was predominantly induced by Cd administration in the target tissues of Cd toxicity, such as the lung, kidney and testis, suggests the possible involvement of osteonectin in Cd intoxication/detoxication mechanisms.
Topics: Amino Acid Sequence; Animals; Blotting, Western; Cadmium; Calcium; Cloning, Molecular; Gene Expression Regulation; Injections, Subcutaneous; Male; Metallothionein; Molecular Sequence Data; Organ Specificity; Osteonectin; RNA, Messenger; Rats; Rats, Wistar; Tissue Distribution
PubMed: 8660135
DOI: 10.1007/s002040050218 -
Current Pharmaceutical Design 2014Cell migration and metastasis greatly contribute to the progression of tumors. Secreted Protein and Rich in Cysteine (SPARC), as a multi-faceted protein, is highly... (Review)
Review
Cell migration and metastasis greatly contribute to the progression of tumors. Secreted Protein and Rich in Cysteine (SPARC), as a multi-faceted protein, is highly expressed in highly metastatic tumors while low or undetectable in less metastatic types with aberrant promoter methylation. In highly metastatic tumors, such as glioblastomas, melanoma, breast cancer and prostate cancer, SPARC promotes bone metastasis and epithelial-mesenchymal transition (EMT). In contrast, this protein acts as an anti-tumor factor in anti-angiogenesis, pro-apoptosis, cell proliferation inhibition and cell cycle arrest in less metastatic tumors, such as neuroblastoma, ovarian cancer, pancreatic cancer, colorectal cancer and gastric cancer. Here, we summarize and analyze the paradoxical role of SPARC in different tumors. We believe that further studies on truncated, alternative splicing variants and signal peptide of SPARC are required to elucidate the distinct effects. Most notably, SPARC variants probably play a crucial role in regulation of transforming growth factor beta (TGF-β) induced EMT. This review also provides strategies to target or use SPARC (full-length, truncated and splicing variants) for therapeutic purposes.
Topics: Humans; Neoplasm Metastasis; Neoplasms; Osteonectin
PubMed: 24947586
DOI: 10.2174/1381612820666140619123255 -
The Breast Journal 2010The purpose of this study was to characterize the immunohistochemical distribution of secreted protein acidic and rich in cystein (SPARC) in benign and malignant breast...
The purpose of this study was to characterize the immunohistochemical distribution of secreted protein acidic and rich in cystein (SPARC) in benign and malignant breast tumors of different histologic types and define its association with the outcome of invasive ductal carcinoma (IDC) patients. A total of 286 samples of benign and malignant breast lesions between 1994 and 2005 were retrieved from National Taiwan University Hospital. Up to 11 years clinical follow-up data were available for 185 patients with IDC. Immunohistochemistry staining with SPARC was performed in tissue microarray or whole section. The association of expression of SPARC and cumulative overall survival of IDC patients were analyzed using Kaplan-Meier survival analysis and Cox regression analysis. Secreted protein acidic and rich in cystein was not expressed in benign breast phylloides and all benign breast tumors, while expressed in 17.2% of IDC, 85% of metaplastic carcinoma of the breast (MCB), and all malignant breast phylloides. Secreted protein acidic and rich in cystein was strongly expressed in mesenchymal components of MCB and expression levels in epithelial components were variable. The correlation of positive expression of SPARC and poor long-term survival in IDC is significant (p = 0.004). Individuals with positive SPARC expression had 2.34 times higher hazard of death compared with those with negative SPARC expression after adjusting for factors including positive lymph node, TNM tumor stage, estrogen receptor, and progesterone receptor. Secreted protein acidic and rich in cystein may be useful as a prognostic indicator for IDC.
Topics: Breast Neoplasms; Carcinoma, Ductal, Breast; Female; Humans; Immunohistochemistry; Neoplasm Staging; Osteonectin; Proportional Hazards Models
PubMed: 20210803
DOI: 10.1111/j.1524-4741.2009.00899.x -
Journal of Cellular Biochemistry Jan 2014There is a growing socioeconomic recognition that clinical bone diseases such as bone infections, bone tumors and osteoporotic bone loss mainly associated with ageing,... (Review)
Review
There is a growing socioeconomic recognition that clinical bone diseases such as bone infections, bone tumors and osteoporotic bone loss mainly associated with ageing, are major issues in today's society. SPARC (secreted protein, acidic and rich in cysteine), a matricellular glycoprotein, may be a promising therapeutic target for preventing or treating bone-related diseases. In fact, SPARC is associated with tissue remodeling, repair, development, cell turnover, bone mineralization and may also participate in growth and progression of tumors, namely cancer-related bone metastasis. Yet, the function of SPARC in such biological processes is poorly understood and controversial. The main objective of this work is to review the current knowledge related to the activity of SPARC in bone remodeling, tumorigenesis, and bone metastasis. Progress in understanding SPARC biology may provide novel strategies for bone regeneration and the development of anti-angiogenic, anti-proliferative, or counter-adhesive treatments specifically against bone metastasis.
Topics: Animals; Bone Neoplasms; Bone Remodeling; Humans; Neoplasms; Osteonectin
PubMed: 24038053
DOI: 10.1002/jcb.24649 -
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 -
Anatomical Record (Hoboken, N.J. : 2007) Jun 2020Matricellular proteins are secreted proteins that, among other functions, can contribute to extracellular matrix (ECM) assembly including modulation of cell:ECM... (Review)
Review
Matricellular proteins are secreted proteins that, among other functions, can contribute to extracellular matrix (ECM) assembly including modulation of cell:ECM interactions. Recent discoveries have indicated a fundamental role for the ECM in the regulation of inflammatory responses including cell extravasation and recruitment, immune cell differentiation, polarization, activation, and retention in tissues. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular collagen-binding protein implicated in fibrillar collagen assembly in the ECM of connective tissue as well as in basal lamina organization. Functions of SPARC in modulating cell adhesion events are also reported. Studies of phenotypic responses observed in SPARC-null mice to a variety of injury models have yielded interesting insight into the functional importance of SPARC production and aberrations in ECM structure that occur in the absence of SPARC that influence immune cell behavior and inflammatory pathways. In this review, we will discuss several examples from different tissues in which SPARC-null mice exhibited an inflammatory response distinct from those of SPARC expressing mice and provide insight into novel ECM-dependent mechanisms that influence these responses. Anat Rec, 2019. © 2019 Wiley Periodicals, Inc.
Topics: Animals; Extracellular Matrix; Fibrillar Collagens; Inflammation; Mice; Mice, Knockout; Osteonectin
PubMed: 30980479
DOI: 10.1002/ar.24133 -
Calcified Tissue International May 1992We investigated immunohistologically 160 teeth and dental germs in various stages of tooth development taken from human individuals (13th week of pregnancy to the 24th...
We investigated immunohistologically 160 teeth and dental germs in various stages of tooth development taken from human individuals (13th week of pregnancy to the 24th year of life) to study the osteonectin expression in dental hard tissue. In the course of dentinogenesis, the predentin, the odontoblasts, and their cell processes show a positive osteonectin staining reaction. During cementogenesis, osteonectin is synthesized by cement-producing fibroblasts, cementoblasts, and cementocytes. The expression of osteonectin during dentinogenesis and cementogenesis is closely related to the development of the respective calcified tissue. All cells of the inner and outer enamel epithelium, the cells of the stratum reticulare and stratum intermedium, the ameloblasts, and the enamel substance are osteonectin negative, just as dentin and cement are. The results of this study indicate one important physiological role of osteonectin as a protein associated with the formation of collagen containing mineralizing tissues like human bone, as well as human dentin and cement.
Topics: Adolescent; Adult; Amelogenesis; Child; Child, Preschool; Dental Cementum; Dentinogenesis; Fetus; Fibroblasts; Humans; Immunohistochemistry; Infant; Infant, Newborn; Osteonectin; Tooth
PubMed: 1596782
DOI: 10.1007/BF00296779 -
Journal of Anatomy Feb 1989Osteonectin/SPARC was most abundantly present in adherent osseous tissue of the cartilage explants. In cartilage explants with ossification fronts, it appears to be...
Osteonectin/SPARC was most abundantly present in adherent osseous tissue of the cartilage explants. In cartilage explants with ossification fronts, it appears to be present in hypertrophic chondroblasts and in the mineralised extracellular cartilage matrix. In a number of cartilage explants it could be demonstrated in the fibroblastic cells of the perichondrium and, intra- and extracellularly, in cartilage located adjacent to the perichondrium. In young mandibular condylar cartilage (20 days post-conception up to 7 days of age) osteonectin/SPARC was characteristically present in the transitional zone, a small area of differentiating skeletoblasts. In cartilage, osteonectin/SPARC might play a role in the process of mineralisation and subsequent replacement by bone. It seems to be an important marker of skeletal differentiation processes.
Topics: Animals; Cartilage; Fluorescent Antibody Technique; Mandibular Condyle; Osteonectin; Rats; Rats, Inbred Strains; Ribs
PubMed: 2681109
DOI: No ID Found -
Biomedicine & Pharmacotherapy =... Sep 2022Secreted protein acidic and rich in cysteine (SPARC), also known as osteonectin or BM-40, is a matricellular protein involved in several biological processes including... (Review)
Review
Secreted protein acidic and rich in cysteine (SPARC), also known as osteonectin or BM-40, is a matricellular protein involved in several biological processes including cell adhesion, growth factor availability, extracellular matrix remodeling and immune-regulation. SPARC has also been associated with a variety of diseases including diabetes, colon cancer, and leukemia. The expression of SPARC in different diseases exhibits some degree of ambiguity, especially in hemopathies. Herein, we review the current expression and effects of SPARC in various hematologic disorders with respect to nanoparticle albumin bound innovative therapies and related diagnostic research, providing a clinical perspective on the use of NAB technology in the frontier treatment of hematologic diseases.
Topics: Albumins; Cell Adhesion; Extracellular Matrix; Hematologic Diseases; Hematologic Neoplasms; Humans; Osteonectin
PubMed: 36076604
DOI: 10.1016/j.biopha.2022.113519