Proteomic profiling of the cancer microenvironment by antibody arrays.
Critical changes in protein expression that enable tumors to initiate and progress originate in the local tissue microenvironment, and there are increasing indications that these microenvironmental alterations in protein expression play critical roles in shaping and directing this process. As a model to better understand how patterns of protein expression shape the tissue microenvironment, we analyzed protein expression in tissue derived from squamous cell carcinoma of the oral cavity through an antibody microarray approach for high-throughput proteomic analysis. Utilizing laser capture microdissection to procure total protein from specific microscopic cellular populations, we demonstrate that quantitative, and potentially qualitative, differences in expression patterns of multiple proteins within epithelial cells reproducibly correlate with oral cavity tumor progression. Furthermore, differential expression of multiple proteins was also found in stromal cells surrounding and adjacent to regions of diseased epithelium that directly correlated with tumor progression of the epithelium. Most of the proteins identified in both cell types are involved in signal transduction pathways, thus we hypothesize that extensive molecular communication involving complex cellular signaling between epithelium and stroma play a key role in driving oral cavity cancer progression.
Knezevic
V
V
Cancer Genome Anatomy Project, National Cancer Institute, NIH, Bethesda, MD, USA.
Leethanakul
C
C
Bichsel
V E
VE
Worth
J M
JM
Prabhu
V V
VV
Gutkind
J S
JS
Liotta
L A
LA
Munson
P J
PJ
Petricoin
E F
EF
Krizman
D B
DB
D000912:Antibodies, Neoplasm / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D004210:Dissection; D004591:Electrophoresis, Polyacrylamide Gel; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007834:Lasers; D009062:Mouth Neoplasms / Q000276:immunology / Q000378:metabolism; D009363:Neoplasm Proteins / Q000276:immunology* / Q000378:metabolism*; D018307:Neoplasms, Squamous Cell / Q000276:immunology / Q000378:metabolism; D020543:Proteome / Q000378:metabolism*
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D009363:Neoplasm Proteins; D020543:Proteome