Anti-angiogenic SPARC peptides inhibit progression of neuroblastoma tumors
<p>Abstract</p> <p>Background</p> <p>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 fo...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2010-06-01
|
| Series: | Molecular Cancer |
| Online Access: | http://www.molecular-cancer.com/content/9/1/138 |
| _version_ | 1818212502228434944 |
|---|---|
| author | Tian Yufeng Yang Qiwei Leonhardt Payton T Spitz Jared A Peddinti Radhika Guerrero Lisa J Chlenski Alexandre Salwen Helen R Cohn Susan L |
| author_facet | Tian Yufeng Yang Qiwei Leonhardt Payton T Spitz Jared A Peddinti Radhika Guerrero Lisa J Chlenski Alexandre Salwen Helen R Cohn Susan L |
| author_sort | Tian Yufeng |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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 <it>in vitro </it>and <it>in vivo</it>, 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.</p> <p>Conclusion</p> <p>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.</p> |
| first_indexed | 2024-12-12T05:49:25Z |
| format | Article |
| id | doaj.art-4cae797d6a074b7a909d23a2ae505381 |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-12-12T05:49:25Z |
| publishDate | 2010-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-4cae797d6a074b7a909d23a2ae5053812022-12-22T00:35:43ZengBMCMolecular Cancer1476-45982010-06-019113810.1186/1476-4598-9-138Anti-angiogenic SPARC peptides inhibit progression of neuroblastoma tumorsTian YufengYang QiweiLeonhardt Payton TSpitz Jared APeddinti RadhikaGuerrero Lisa JChlenski AlexandreSalwen Helen RCohn Susan L<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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 <it>in vitro </it>and <it>in vivo</it>, 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.</p> <p>Conclusion</p> <p>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.</p>http://www.molecular-cancer.com/content/9/1/138 |
| spellingShingle | Tian Yufeng Yang Qiwei Leonhardt Payton T Spitz Jared A Peddinti Radhika Guerrero Lisa J Chlenski Alexandre Salwen Helen R Cohn Susan L Anti-angiogenic SPARC peptides inhibit progression of neuroblastoma tumors Molecular Cancer |
| title | Anti-angiogenic SPARC peptides inhibit progression of neuroblastoma tumors |
| title_full | Anti-angiogenic SPARC peptides inhibit progression of neuroblastoma tumors |
| title_fullStr | Anti-angiogenic SPARC peptides inhibit progression of neuroblastoma tumors |
| title_full_unstemmed | Anti-angiogenic SPARC peptides inhibit progression of neuroblastoma tumors |
| title_short | Anti-angiogenic SPARC peptides inhibit progression of neuroblastoma tumors |
| title_sort | anti angiogenic sparc peptides inhibit progression of neuroblastoma tumors |
| url | http://www.molecular-cancer.com/content/9/1/138 |
| work_keys_str_mv | AT tianyufeng antiangiogenicsparcpeptidesinhibitprogressionofneuroblastomatumors AT yangqiwei antiangiogenicsparcpeptidesinhibitprogressionofneuroblastomatumors AT leonhardtpaytont antiangiogenicsparcpeptidesinhibitprogressionofneuroblastomatumors AT spitzjareda antiangiogenicsparcpeptidesinhibitprogressionofneuroblastomatumors AT peddintiradhika antiangiogenicsparcpeptidesinhibitprogressionofneuroblastomatumors AT guerrerolisaj antiangiogenicsparcpeptidesinhibitprogressionofneuroblastomatumors AT chlenskialexandre antiangiogenicsparcpeptidesinhibitprogressionofneuroblastomatumors AT salwenhelenr antiangiogenicsparcpeptidesinhibitprogressionofneuroblastomatumors AT cohnsusanl antiangiogenicsparcpeptidesinhibitprogressionofneuroblastomatumors |