Proteomic Analysis of Neuroblastoma Microenvironment: Effect of the Host–Tumor Interaction on Disease Progression

肿瘤微环境 神经母细胞瘤 癌症研究 体内 蛋白质组学 肿瘤进展 生物 疾病 阶段(地层学) 癌症 细胞培养 医学 病理 肿瘤细胞 遗传学 基因 古生物学
作者
Katharyn E. Turner,Hari R. Kumar,Derek J. Hoelz,Xiaoling Zhong,Frederick J. Rescorla,Robert J. Hickey,Linda H. Malkas,John A. Sandoval
出处
期刊:Journal of Surgical Research [Elsevier]
卷期号:156 (1): 116-122 被引量:6
标识
DOI:10.1016/j.jss.2009.02.019
摘要

Background Children with advanced-stage neuroblastoma (NB) traditionally experience poor outcomes. Because early detection of advanced-stage disease may impact survival, finding new targets for early diagnosis is crucial. Evidence suggests the tumor microenvironment may have profound effects on cancer progression. Methods As little is known concerning the NB-host microenvironment, this study applied proteomic techniques, two-dimensional polyacrylamide gel electrophoresis (2D PAGE) combined with matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry to determine protein differences between cell cultured NB and tumors grown in mice for 2, 4, and 5 wk. Results We found an increase in proteins in cultured NB compared with implanted mouse tumors during tumor progression. Additionally, analyzing in vivo tumors to cultured NB, we observed less expressed proteins. However, 16 out of 19 proteins were of mouse origin, thus inferring host-derived factors contributing to tumor growth. Conclusion We show that the dynamic relationship between NB and host microenvironment is important for tumor growth and better understanding of this milieu maybe relevant towards finding unique approaches for identifying advanced-stage disease. Children with advanced-stage neuroblastoma (NB) traditionally experience poor outcomes. Because early detection of advanced-stage disease may impact survival, finding new targets for early diagnosis is crucial. Evidence suggests the tumor microenvironment may have profound effects on cancer progression. As little is known concerning the NB-host microenvironment, this study applied proteomic techniques, two-dimensional polyacrylamide gel electrophoresis (2D PAGE) combined with matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry to determine protein differences between cell cultured NB and tumors grown in mice for 2, 4, and 5 wk. We found an increase in proteins in cultured NB compared with implanted mouse tumors during tumor progression. Additionally, analyzing in vivo tumors to cultured NB, we observed less expressed proteins. However, 16 out of 19 proteins were of mouse origin, thus inferring host-derived factors contributing to tumor growth. We show that the dynamic relationship between NB and host microenvironment is important for tumor growth and better understanding of this milieu maybe relevant towards finding unique approaches for identifying advanced-stage disease.
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