Kinase substrate protein microarray analysis of human colon cancer and hepatic metastasis.
BACKGROUND
Liver metastases represent the major determinant of survival in patients with colorectal cancer (CRC). In cases with unresectable liver disease, more effective agents are needed, since chemotherapy achieves median survival of only 15 months. Protein kinases coordinate complex functions that are often disregulated in cancer and are therefore considered important targets for molecular therapeutics. In this study, we investigated the phosphoproteomic status of different protein kinases in primary CRC and in liver metastases.


METHODS
The status of 29 key endpoints was evaluated using reverse phase protein array on laser capture microdissected neoplastic cells from five primary CRCs without metastases, three patient-matched primary CRCs and synchronous liver metastases and five CRC metachronous liver metastases.


RESULTS
Unsupervised hierarchical two-way clustering analysis showed an entirely different phosphoproteomic profile in primary CRCs compared to liver metastases. This difference was observed also in primary and metastatic patient-matched lesions.


CONCLUSIONS
Our findings of different signaling pathways between primary and metastatic CRC suggest a possible microenvironment effect, and emphasize the need to perform molecular network analysis of metastatic tissue when molecular targeting is considered.
Belluco
Claudio
C
Department of Oncological and Surgical Science, Surgery Branch, University of Padova, Padova, Italy. claudio.belluco@unipd.it
Mammano
Enzo
E
Petricoin
Emanuel
E
Prevedello
Luca
L
Calvert
Valerie
V
Liotta
Lance
L
Nitti
Donato
D
Lise
Mario
M
D016000:Cluster Analysis; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000556:secondary*; D010770:Phosphotransferases / Q000378:metabolism*; D040081:Protein Array Analysis; D013379:Substrate Specificity
D010770:Phosphotransferases