Protein pathway activation mapping of colorectal metastatic progression reveals metastasis-specific network alterations.
The mechanism by which tissue microecology influences invasion and metastasis is largely unknown. Recent studies have indicated differences in the molecular architecture of the metastatic lesion compared to the primary tumor, however, systemic analysis of the alterations within the activated protein signaling network has not been described. Using laser capture microdissection, protein microarray technology, and a unique specimen collection of 34 matched primary colorectal cancers (CRC) and synchronous hepatic metastasis, the quantitative measurement of the total and activated/phosphorylated levels of 86 key signaling proteins was performed. Activation of the EGFR-PDGFR-cKIT network, in addition to PI3K/AKT pathway, was found uniquely activated in the hepatic metastatic lesions compared to the matched primary tumors. If validated in larger study sets, these findings may have potential clinical relevance since many of these activated signaling proteins are current targets for molecularly targeted therapeutics. Thus, these findings could lead to liver metastasis specific molecular therapies for CRC.
Center for Applied Proteomics and Molecular Medicine, George Mason University, 10900 University Blvd., Manassas, VA, 20110, USA.
Alessandra
A
Silvestri
Valerie
V
Calvert
Claudio
C
Belluco
Michael
M
Lipsky
Ruggero
R
De Maria
Jianghong
J
Deng
Alfonso
A
Colombatti
Francesco
F
De Marchi
Donato
D
Nitti
Enzo
E
Mammano
Lance
L
Liotta
Emanuel
E
Petricoin
Mariaelena
M
Pierobon
D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D010766:Phosphorylation; D040081:Protein Array Analysis
D009363:Neoplasm Proteins