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Advanced Animal Model of Colorectal Metastasis in Liver: Imaging Techniques and Properties of Metastatic Clones
11:43

Advanced Animal Model of Colorectal Metastasis in Liver: Imaging Techniques and Properties of Metastatic Clones

Published on: November 30, 2016

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

Alessandra Silvestri1, Valerie Calvert, Claudio Belluco

  • 1Center for Applied Proteomics and Molecular Medicine, George Mason University, 10900 University Blvd., Manassas, VA, 20110, USA.

Clinical & Experimental Metastasis
|October 12, 2012
PubMed

Insights

Researchers identified unique activated signaling pathways in liver metastasis of colorectal cancer (CRC) compared to primary tumors. These findings could inform new liver metastasis-specific therapies for CRC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Metastasis

Background:

  • The influence of tissue microecology on cancer invasion and metastasis remains poorly understood.
  • Differences in molecular architecture exist between primary tumors and metastatic lesions, but signaling network alterations are not well-described.

Purpose of the Study:

  • To systematically analyze alterations in activated protein signaling networks between primary colorectal cancers (CRC) and synchronous hepatic metastases.
  • To identify specific molecular targets for potential liver metastasis-specific therapies.

Main Methods:

  • Utilized laser capture microdissection and protein microarray technology.
  • Quantitatively measured total and activated/phosphorylated levels of 86 key signaling proteins.
  • Analyzed 34 matched pairs of primary CRC and hepatic metastasis specimens.

Main Results:

  • Identified unique activation of the EGFR-PDGFR-cKIT network in hepatic metastatic lesions compared to primary tumors.
  • Observed unique activation of the PI3K/AKT pathway in hepatic metastatic lesions.
  • Found distinct protein signaling profiles between primary CRC and liver metastases.

Conclusions:

  • Specific signaling pathways are uniquely activated in colorectal cancer liver metastases.
  • These activated pathways, including EGFR-PDGFR-cKIT and PI3K/AKT, represent potential targets for novel therapeutics.
  • Findings suggest the possibility of developing liver metastasis-specific molecular therapies for CRC.

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