A pilot study exploring the molecular architecture of the tumor microenvironment in human prostate cancer using laser capture microdissection and reverse phase protein microarray

被引:21
|
作者
Pin, Elisa [1 ,2 ]
Stratton, Steven [3 ]
Belluco, Claudio [4 ]
Liotta, Lance [1 ]
Nagle, Ray [3 ]
Hodge, K. Alex [1 ]
Deng, Jianghong [1 ]
Dong, Ting [1 ]
Baldelli, Elisa [1 ]
Petricoin, Emanuel [1 ]
Pierobon, Mariaelena [1 ]
机构
[1] George Mason Univ, Ctr Appl Prote & Mol Med, 10920 George Mason Circle,Room 2016, Manassas, VA 20110 USA
[2] Natl Canc Inst, Div Expt Oncol 2, CRO IRCCS, Aviano, Italy
[3] Univ Arizona, Div Canc Prevent & Control, Ctr Canc, Tucson, AZ USA
[4] Natl Canc Inst, Dept Surg Oncol, CRO IRCCS, Aviano, Italy
关键词
Prostate cancer; Laser capture microdissection; Reverse phase protein microarray; Tumor microenvironment; Kinase signaling; Cross-talk; INFILTRATING LYMPHOCYTES; PHOSPHOPROTEIN STABILITY; SIGNALING ACTIVATION; STROMAL INTERACTIONS; CLINICAL TISSUE; BREAST-CANCER; SURVIVAL; LUNG; INHIBITION; EXPRESSION;
D O I
10.1016/j.molonc.2016.09.007
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The cross-talk between tumor epithelium and surrounding stromal/immune microenvironment is essential to sustain tumor growth and progression and provides new opportunities for the development of targeted treatments focused on disrupting the tumor ecology. Identification of novel approaches to study these interactions is of primary importance. Using laser capture microdissection (LCM) coupled with reverse phase protein microarray (RPPA) based protein signaling activation mapping we explored the molecular interconnection between tumor epithelium and surrounding stromal microenvironment in 18 prostate cancer (PCa) specimens. Four specimen-matched cellular compartments (normal-appearing epithelium and its adjacent stroma, and malignant epithelium and its adjacent stroma) were isolated for each case. The signaling network analysis of the four compartments unraveled a number of molecular mechanisms underlying the communication between tumor cells and stroma in the context of the tumor microenvironment. In particular, differential expression of inflammatory mediators like IL-8 and IL-10 by the stroma cells appeared to modulate specific cross-talks between the tumor cells and surrounding microenvironment. (C) 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:1585 / 1594
页数:10
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