EFEMP1 suppresses malignant glioma growth and exerts its action within the tumor extracellular compartment
<p>Abstract</p> <p>Purpose</p> <p>There are conflicting reports regarding the function of EFEMP1 in different cancer types. In this study, we sought to evaluate the role of EFEMP1 in malignant glioma biology.</p> <p>Experimental Design</p> <p>Rea...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2011-09-01
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| Series: | Molecular Cancer |
| Online Access: | http://www.molecular-cancer.com/content/10/1/123 |
| _version_ | 1818234663886389248 |
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| author | Hess Kenneth R Yu Liping Hamamura Mark Hsu Nelson Alkafeef Selma Ro Daniel I Mathews Marlon S Chaturbedi Abhishek Nelson Jodi Zhang Qinghua Siegel Eric Pioli Peter Hu Yuanjie Tromberg Bruce J Linskey Mark E Zhou Yi-Hong |
| author_facet | Hess Kenneth R Yu Liping Hamamura Mark Hsu Nelson Alkafeef Selma Ro Daniel I Mathews Marlon S Chaturbedi Abhishek Nelson Jodi Zhang Qinghua Siegel Eric Pioli Peter Hu Yuanjie Tromberg Bruce J Linskey Mark E Zhou Yi-Hong |
| author_sort | Hess Kenneth R |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Purpose</p> <p>There are conflicting reports regarding the function of EFEMP1 in different cancer types. In this study, we sought to evaluate the role of EFEMP1 in malignant glioma biology.</p> <p>Experimental Design</p> <p>Real-time qRT-PCR was used to quantify <it>EFEMP1 </it>expression in 95 glioblastoma multiforme (GBM). Human high-grade glioma cell lines and primary cultures were engineered to express ectopic EFEMP1, a small hairpin RNA of EFEMP1, or treated with exogenous recombinant EFEMP1 protein. Following treatment, growth was assayed both <it>in vitro </it>and <it>in vivo </it>(subcutaneous (s.c.) and intracranial (i.c.) xenograft model systems).</p> <p>Results</p> <p>Cox regression revealed that EFEMP1 is a favorable prognostic marker for patients with GBM. Over-expression of EFEMP1 eliminated tumor development and suppressed angiogenesis, cell proliferation, and VEGFA expression, while the converse was true with knock-down of endogenous EFEMP1 expression. The EFEMP1 suppression of tumor onset time was nearly restored by ectopic VEGFA expression; however, overall tumor growth rate remained suppressed. This suggested that inhibition of angiogenesis was only partly responsible for EFEMP1's impact on glioma development. In glioma cells that were treated by exogenous EFEMP1 protein or over-expressed endogenous EFEMP1, the EGFR level was reduced and AKT signaling activity attenuated. Mixing of EFEMP1 protein with cells prior to s.c. and i.c. implantations or injection of the protein around the established s.c. xenografts, both significantly suppressed tumorigenicity.</p> <p>Conclusions</p> <p>Overall, our data reveals that EEFEMP1 suppresses glioma growth <it>in vivo</it>, both by modulating the tumor extracellular microenvironment and by altering critical intracellular oncogenic signaling pathways.</p> |
| first_indexed | 2024-12-12T11:41:40Z |
| format | Article |
| id | doaj.art-cd0ddeda303c4bbeb97723e9dcbf42b3 |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-12-12T11:41:40Z |
| publishDate | 2011-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-cd0ddeda303c4bbeb97723e9dcbf42b32022-12-22T00:25:31ZengBMCMolecular Cancer1476-45982011-09-0110112310.1186/1476-4598-10-123EFEMP1 suppresses malignant glioma growth and exerts its action within the tumor extracellular compartmentHess Kenneth RYu LipingHamamura MarkHsu NelsonAlkafeef SelmaRo Daniel IMathews Marlon SChaturbedi AbhishekNelson JodiZhang QinghuaSiegel EricPioli PeterHu YuanjieTromberg Bruce JLinskey Mark EZhou Yi-Hong<p>Abstract</p> <p>Purpose</p> <p>There are conflicting reports regarding the function of EFEMP1 in different cancer types. In this study, we sought to evaluate the role of EFEMP1 in malignant glioma biology.</p> <p>Experimental Design</p> <p>Real-time qRT-PCR was used to quantify <it>EFEMP1 </it>expression in 95 glioblastoma multiforme (GBM). Human high-grade glioma cell lines and primary cultures were engineered to express ectopic EFEMP1, a small hairpin RNA of EFEMP1, or treated with exogenous recombinant EFEMP1 protein. Following treatment, growth was assayed both <it>in vitro </it>and <it>in vivo </it>(subcutaneous (s.c.) and intracranial (i.c.) xenograft model systems).</p> <p>Results</p> <p>Cox regression revealed that EFEMP1 is a favorable prognostic marker for patients with GBM. Over-expression of EFEMP1 eliminated tumor development and suppressed angiogenesis, cell proliferation, and VEGFA expression, while the converse was true with knock-down of endogenous EFEMP1 expression. The EFEMP1 suppression of tumor onset time was nearly restored by ectopic VEGFA expression; however, overall tumor growth rate remained suppressed. This suggested that inhibition of angiogenesis was only partly responsible for EFEMP1's impact on glioma development. In glioma cells that were treated by exogenous EFEMP1 protein or over-expressed endogenous EFEMP1, the EGFR level was reduced and AKT signaling activity attenuated. Mixing of EFEMP1 protein with cells prior to s.c. and i.c. implantations or injection of the protein around the established s.c. xenografts, both significantly suppressed tumorigenicity.</p> <p>Conclusions</p> <p>Overall, our data reveals that EEFEMP1 suppresses glioma growth <it>in vivo</it>, both by modulating the tumor extracellular microenvironment and by altering critical intracellular oncogenic signaling pathways.</p>http://www.molecular-cancer.com/content/10/1/123 |
| spellingShingle | Hess Kenneth R Yu Liping Hamamura Mark Hsu Nelson Alkafeef Selma Ro Daniel I Mathews Marlon S Chaturbedi Abhishek Nelson Jodi Zhang Qinghua Siegel Eric Pioli Peter Hu Yuanjie Tromberg Bruce J Linskey Mark E Zhou Yi-Hong EFEMP1 suppresses malignant glioma growth and exerts its action within the tumor extracellular compartment Molecular Cancer |
| title | EFEMP1 suppresses malignant glioma growth and exerts its action within the tumor extracellular compartment |
| title_full | EFEMP1 suppresses malignant glioma growth and exerts its action within the tumor extracellular compartment |
| title_fullStr | EFEMP1 suppresses malignant glioma growth and exerts its action within the tumor extracellular compartment |
| title_full_unstemmed | EFEMP1 suppresses malignant glioma growth and exerts its action within the tumor extracellular compartment |
| title_short | EFEMP1 suppresses malignant glioma growth and exerts its action within the tumor extracellular compartment |
| title_sort | efemp1 suppresses malignant glioma growth and exerts its action within the tumor extracellular compartment |
| url | http://www.molecular-cancer.com/content/10/1/123 |
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