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Metastatic signature in lung cancer is associated with sensitivity to anti‐integrin α V monoclonal antibody intetumumab
Author(s) -
Liu Huiqing,
Park Jaehong,
Manning Carol,
Goehlmann Hinrich W.H.,
Marshall Deborah J.
Publication year - 2014
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22145
Subject(s) - lung cancer , microrna , metastasis , biology , cancer research , gene signature , monoclonal antibody , cancer , immunology , pathology , gene , gene expression , antibody , medicine , genetics
Intetumumab is a fully human monoclonal antibody that inhibits α v integrins. It has been shown in in vitro assays to effectively inhibit cell viability, metastasis, and adhesion of human cancer cells and endothelial cells. However, the response to Intetumumab varies in different tumor cell lines. To understand the growth inhibition mechanism of Intetumumab and to identify a molecular signature that can predict sensitivity, we focused on lung cancer cell lines and performed a series of proliferation assays. We then assessed the global gene expression profiles, DNA copy number variations, and microRNA profiles from a total of 23 lung cancer lines. The results revealed that lung cancer sensitivity to Intetumumab is associated with several chromosomal alterations, particularly genetic loss at chromosome arm 19p, which resulted in gene expression changes. We identified a genetic signature that can be used to predict Intetumumab sensitivity for lung cancer cell lines. Independently, microRNA analysis revealed a panel of signature microRNAs that includes several markers of epithelial to mesenchymal transition and tumor metastasis such as miR‐200 family and miR‐205. Both the genetic and microRNA signatures provide insights into the potential mechanism of Intetumumab activity and serve as the first step to develop a patient stratification strategy for Intetumumab therapy in lung cancer. © 2014 Wiley Periodicals, Inc.