Abstract
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.
Keywords: Bone metastasis, EMT, highly metastatic tumors, less metastatic tumors, SPARC.
Current Pharmaceutical Design
Title:SPARC in Tumor Pathophysiology and as a Potential Therapeutic Target
Volume: 20 Issue: 39
Author(s): Jianguo Feng and Liling Tang
Affiliation:
Keywords: Bone metastasis, EMT, highly metastatic tumors, less metastatic tumors, SPARC.
Abstract: 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.
Export Options
About this article
Cite this article as:
Feng Jianguo and Tang Liling, SPARC in Tumor Pathophysiology and as a Potential Therapeutic Target, Current Pharmaceutical Design 2014; 20 (39) . https://dx.doi.org/10.2174/1381612820666140619123255
DOI https://dx.doi.org/10.2174/1381612820666140619123255 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Synthesized 2-Trifluoromethylquinazolines and Quinazolinones Protect BV2 and N2a Cells against LPS- and H<sub>2</sub>O<sub>2</sub>-induced Cytotoxicity
Medicinal Chemistry Metal and Inflammatory Targets for Alzheimers Disease
Current Drug Targets Multifunctional Proteins in Tumorigenesis: Aminoacyl-tRNA Synthetases and Translational Components
Current Proteomics The NK-1 Receptor is Involved in the Antitumoural Action of L-733,060 and in the Mitogenic Action of Substance P on Human Pancreatic Cancer Cell Lines
Letters in Drug Design & Discovery Regulatory Role of Anesthetics on Heme Oxygenase-1
Current Drug Targets Netrin and DCC: Axon Guidance Regulators at the Intersection of Nervous System Development and Cancer
Current Drug Targets Machine Learning Based Pattern Recognition Applied to Microarray Data
Combinatorial Chemistry & High Throughput Screening VIP in Inflammatory Bowel Disease: State of the Art
Endocrine, Metabolic & Immune Disorders - Drug Targets Neuropeptide FF Inhibits LPS-Mediated Osteoclast Differentiation of RAW264.7 Cells
Protein & Peptide Letters Exploring Mechanisms of MicroRNA Downregulation in Cancer
MicroRNA Novel Therapeutic Strategies for Dementia
CNS & Neurological Disorders - Drug Targets Hypoxia-Inducible Factor-1 (HIF-1): A Potential Target for Intervention in Ocular Neovascular Diseases
Current Drug Targets New Generation of Liposomal Drugs for Cancer
Anti-Cancer Agents in Medicinal Chemistry Mesenchymal Stromal Cell Therapy for Cardio Renal Disorders
Current Pharmaceutical Design Targeting the Pleiotrophin/Receptor Protein Tyrosine Phosphatase β /ζ Signaling Pathway to Limit Neurotoxicity Induced by Drug Abuse
Mini-Reviews in Medicinal Chemistry Multimodality Imaging of RNA Interference
Current Medicinal Chemistry Prion Protein Peptides as Vaccines
Mini-Reviews in Medicinal Chemistry Targeting Indoleamine 2,3-dioxygenase (IDO) to Counteract Tumour- Induced ImmuneDysfunction: From Biochemistry to Clinical Development
Endocrine, Metabolic & Immune Disorders - Drug Targets Pharmacologic Activation of p53 by Small-Molecule MDM2 Antagonists
Current Pharmaceutical Design The Brain Protective Effect of rTMS (Repetitive Transcranial Magnetic Stimulation) in Depression: A Mini-Review in Animal Studies
Medicinal Chemistry