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Rational Selection of Antigens for Targeted Therapy of Liver Metastases
Author(s) -
TURTOI Andrei,
BLOMME Arnaud,
CASTRONOVO Vincent
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.397.6
Subject(s) - colorectal cancer , antigen , medicine , cancer research , proteome , oncology , cancer , biology , immunology , bioinformatics
Patients suffering from liver metastases are diagnosed late and have a poor outcome. Targeted therapies are gaining a major stake in current and future treatment options. However, the malignant lesions are heterogeneous in nature offering niches for cancer cells causing treatment resistance and relapse. Therefore, a rational strategy is needed to select targetable antigens that would overcome this intra‐tumoral heterogeneity. Here we generated a quantitative picture of the proteome heterogeneity in colorectal carcinoma liver metastases. We focus on membrane bound and extracellular proteins and show the differential distribution of novel targets and antigens against which the antibodies are already involved in clinical trials or treatment of liver metastases. Extensive clustering and validation experiments highlight novel markers that offer the potential to homogeneously cover the metastatic lesion and become better targets. Two such antigens, LTBP2 and TGFBI are selected for functional analysis in colorectal carcinoma cells. In vitro and in vivo experiments show that both proteins are relevant for migration and proliferation capacities of cancer cells. Their depletion leads to significant inhibition of tumor growth, crystalizing them as bona fide targets for development of anti‐metastases therapies. This work is funded by FP7 (ADAMANT) the European Union project, Univeristy of Liège & the ARC (IDEA) project, Belgium.