EFEMP1 suppresses malignant glioma growth and exerts its action within the tumor extracellular compartment

Molecular Cancer

Research

Bruce J Tromberg¹  Selma Alkafeef²  Yuanjie Hu²  Peter Dion Pioli²  Yi-Hong Zhou³  Eric Siegel⁴  Kenneth R Hess⁵  Qinghua Zhang⁶  Mark E Linskey⁷  Daniel I Ro⁷  Nelson Hsu⁷  Marlon S Mathews⁷  Jodi Nelson⁷  Abhishek Chaturbedi⁷  Mark Hamamura⁸  Liping Yu⁹ 

[1] Beckman Laser Institute, University of California Irvine, 5171 California Ave., Suite 150, 92697, Irvine, CA, USA;Department of Biological Chemistry, University of California Irvine, 5171 California Ave., Suite 150, 92697, Irvine, CA, USA;Department of Biological Chemistry, University of California Irvine, 5171 California Ave., Suite 150, 92697, Irvine, CA, USA;Neurological Surgery, University of California Irvine, 5171 California Ave., Suite 150, 92697, Irvine, CA, USA;Department of Biostatistics, University of Arkansas for Medical Sciences, 4301 W. Markham St, 72205, Little Rock, AR, USA;Department of Biostatistics, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, 77030, Houston, TX, USA;National Engineering Center for Biochip at Shanghai & Shanghai Biochip Co., Lt, 151 Libing Rd, 201203, Shanghai, China;Neurological Surgery, University of California Irvine, 5171 California Ave., Suite 150, 92697, Irvine, CA, USA;Tu & Yuen Center for Functional Onco-Imaging, University of California Irvine, 5171 California Ave., Suite 150, 92697, Irvine, CA, USA;Ziren Research LLC, 9841 Irvine Center Drive, 92618, Irvine, CA, USA;

关键词: Glioma Cell;    Glioma Cell Line;    Glioma Growth;    VEGFA Isoforms;    Human Malignant Glioma Cell Line;   

DOI  :  10.1186/1476-4598-10-123

 received in 2011-05-26, accepted in 2011-09-28,  发布年份 2011

来源: Springer

【 摘 要 】

PurposeThere 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.Experimental DesignReal-time qRT-PCR was used to quantify EFEMP1 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 in vitro and in vivo (subcutaneous (s.c.) and intracranial (i.c.) xenograft model systems).ResultsCox 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.ConclusionsOverall, our data reveals that EEFEMP1 suppresses glioma growth in vivo, both by modulating the tumor extracellular microenvironment and by altering critical intracellular oncogenic signaling pathways.

【 授权许可】

Unknown   
© Hu et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.