title: Kinase substrate protein microarray analysis of human colon cancer and hepatic metastasis.
abstract: 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.
authors.affiliation: Department of Oncological and Surgical Science, Surgery Branch, University of Padova, Padova, Italy. claudio.belluco@unipd.it
authors.forename: Claudio
authors.initials: C
authors.lastname: Belluco
authors.forename: Enzo
authors.initials: E
authors.lastname: Mammano
authors.forename: Emanuel
authors.initials: E
authors.lastname: Petricoin
authors.forename: Luca
authors.initials: L
authors.lastname: Prevedello
authors.forename: Valerie
authors.initials: V
authors.lastname: Calvert
authors.forename: Lance
authors.initials: L
authors.lastname: Liotta
authors.forename: Donato
authors.initials: D
authors.lastname: Nitti
authors.forename: Mario
authors.initials: M
authors.lastname: Lise
mesh_terms: 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
chemical_list: D010770:Phosphotransferases