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Published on: September 18, 2019
Anti-angiogenic SPARC peptides inhibit progression of neuroblastoma tumors
Alexandre Chlenski1, Lisa J Guerrero, Radhika Peddinti
1Department of Pediatrics, University of Chicago, KCBD Rm. 5100, Chicago, IL 60637, USA.
Background:
New, more effective strategies are needed to treat highly aggressive neuroblastoma. Our laboratory has previously shown that full-length Secreted Protein Acidic and Rich in Cysteine (SPARC) and a SPARC peptide corresponding to the follistatin domain of the protein (FS-E) potently block angiogenesis and inhibit the growth of neuroblastoma tumors in preclinical models. Peptide FS-E is structurally complex and difficult to produce, limiting its potential as a therapeutic in the clinic.
Results:
In this study, we synthesized two smaller and structurally more simple SPARC peptides, FSEN and FSEC, that respectively correspond to the N-and C-terminal loops of peptide FS-E. We show that both peptides FSEN and FSEC have anti-angiogenic activity in vitro and in vivo, although FSEC is more potent. Peptide FSEC also significantly inhibited the growth of neuroblastoma xenografts. Histologic examination demonstrated characteristic features of tumor angiogenesis with structurally abnormal, tortuous blood vessels in control neuroblastoma xenografts. In contrast, the blood vessels observed in tumors, treated with SPARC peptides, were thin walled and structurally more normal. Using a novel method to quantitatively assess blood vessel abnormality we demonstrated that both SPARC peptides induced changes in blood vessel architecture that are consistent with blood vessel normalization.
Conclusion:
Our results demonstrate that SPARC peptide FSEC has potent anti-angiogenic and anti-tumorigenic effects in neuroblastoma. Its simple structure and ease of production indicate that it may have clinical utility in the treatment of high-risk neuroblastoma and other types of pediatric and adult cancers, which depend on angiogenesis.
Insights
New SPARC peptides, FSEN and FSEC, show promise for treating aggressive neuroblastoma by inhibiting tumor growth and normalizing blood vessels. FSEC is particularly effective, offering potential clinical utility for various cancers.
Area of Science:
- Oncology
- Vascular Biology
- Biotechnology
Background:
- Aggressive neuroblastoma requires novel therapeutic strategies.
- Full-length Secreted Protein Acidic and Rich in Cysteine (SPARC) and its follistatin domain peptide (FS-E) inhibit neuroblastoma growth.
- Peptide FS-E's complexity hinders clinical application.
Purpose of the Study:
- To synthesize and evaluate smaller, simpler SPARC peptides (FSEN, FSEC) derived from FS-E.
- To assess the anti-angiogenic and anti-tumorigenic potential of FSEN and FSEC in neuroblastoma models.
Main Methods:
- Synthesis of SPARC peptides FSEN and FSEC.
- In vitro and in vivo assessment of anti-angiogenic activity.
- Evaluation of neuroblastoma xenograft growth inhibition.
- Histologic analysis of tumor vasculature.
- Quantitative assessment of blood vessel abnormality.
Main Results:
- Both FSEN and FSEC peptides demonstrated anti-angiogenic effects in vitro and in vivo.
- Peptide FSEC exhibited more potent anti-angiogenic activity.
- FSEC significantly inhibited neuroblastoma xenograft growth.
- SPARC peptides promoted normalization of tumor blood vessels, reducing tortuosity and improving structure.
Conclusions:
- SPARC peptide FSEC possesses significant anti-angiogenic and anti-tumorigenic properties in neuroblastoma.
- The simplified structure and ease of production of FSEC suggest potential clinical applications.
- FSEC may be a valuable therapeutic agent for high-risk neuroblastoma and other angiogenesis-dependent cancers.
