Protein pathway activation mapping of colorectal metastatic progression reveals metastasis-specific network alterations

Ruggero De Maria Marchiano, Alessandra Silvestri, Valerie Calvert, Claudio Belluco, Michael Lipsky, Jianghong Deng, Alfonso Colombatti, Francesco De Marchi, Donato Nitti, Enzo Mammano, Lance Liotta, Emanuel Petricoin, Mariaelena Pierobon

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)309-316
Number of pages8
JournalCLINICAL & EXPERIMENTAL METASTASIS
DOIs
Publication statusPublished - 2012

Keywords

  • Colorectal cancer
  • Metastasis
  • Protein pathway activation mapping
  • Proteomics
  • Reverse phase protein microarray
  • Tumor microenvironment

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