A pilot study exploring the molecular architecture of the tumor microenvironment in human prostate cancer using laser capture microdissection and reverse phase protein microarray.
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.
Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA; Division of Experimental Oncology 2, CRO-IRCCS, National Cancer Institute, Aviano, Italy.
Elisa
E
Pin
Division of Cancer Prevention and Control, University of Arizona Cancer Center, Tucson, AZ, USA.
Steven
S
Stratton
Department of Surgical Oncology, CRO-IRCCS, National Cancer Institute, Aviano, Italy.
Claudio
C
Belluco
Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA.
Lance
L
Liotta
Division of Cancer Prevention and Control, University of Arizona Cancer Center, Tucson, AZ, USA.
Ray
R
Nagle
Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA.
K Alex
KA
Hodge
Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA.
Jianghong
J
Deng
Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA.
Ting
T
Dong
Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA.
Elisa
E
Baldelli
Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA.
Emanuel
E
Petricoin
Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA. Electronic address: mpierobo@gmu.edu.
Mariaelena
M
Pierobon
D006801:Humans; D016753:Interleukin-10 / Q000032:analysis / Q000378:metabolism; D016209:Interleukin-8 / Q000032:analysis / Q000378:metabolism; D061346:Laser Capture Microdissection; D008297:Male; D010865:Pilot Projects; D011467:Prostate / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D040081:Protein Array Analysis; D060066:Protein Interaction Maps; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D059016:Tumor Microenvironment
C508609:IL10 protein, human; D016209:Interleukin-8; D016753:Interleukin-10
Cross-talk; Kinase signaling; Laser capture microdissection; Prostate cancer; Reverse phase protein microarray; Tumor microenvironment