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The type I insulin-like growth factor receptor regulates cancer metastasis independently of primary tumor growth by promoting invasion and survival
The type I insulin-like growth factor receptor (IGF1R) regulates multiple aspects of malignancy and is the target of several drugs currently in clinical trials. While IGF1R’s role in proliferation and survival is well-studied, the regulation of metastasis by IGF1R is not as clearly delineated. Previ...
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Formato: | Texto |
Lenguaje: | English |
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2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2843625/ https://www.ncbi.nlm.nih.gov/pubmed/19838209 http://dx.doi.org/10.1038/onc.2009.316 |
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author | Sachdev, Deepali Zhang, Xihong Matise, Ilze Gaillard-Kelly, Martine Yee, Douglas |
author_facet | Sachdev, Deepali Zhang, Xihong Matise, Ilze Gaillard-Kelly, Martine Yee, Douglas |
author_sort | Sachdev, Deepali |
collection | PubMed |
description | The type I insulin-like growth factor receptor (IGF1R) regulates multiple aspects of malignancy and is the target of several drugs currently in clinical trials. While IGF1R’s role in proliferation and survival is well-studied, the regulation of metastasis by IGF1R is not as clearly delineated. Previous work showed that disruption of IGF1R signaling via overexpression of a dominant negative IGF1R inhibited metastasis. To establish a clinically applicable approach to inhibition of metastasis by targeting IGF1R, the effect of an inhibitory antibody against IGF1R, EM164 and its humanized version, AVE1642 on metastasis of cancer cells was examined. EM164 and AVE1642 did not affect primary tumor growth of MDA-435A/LCC6 cells but inhibited metastasis of these cells. Consistent with this inhibition in the formation of metastatic nodules, disruption of IGF1R also resulted in a decreased number of circulating tumor cells in blood of tumor-bearing mice. Disruption of IGF1R with a dominant negative construct or antibody inhibited invasion across Matrigel in vitro. When tumor cells were directly injected into the circulation via the lateral tail vein of mice, IGF1R disruption also resulted in significant reduction of pulmonary nodules, suggesting that regulation of invasion is not the only function of IGF1R signaling. Further, disruption of IGF1R rendered cells more susceptible to anoikis. Thus, IGF1R regulated metastasis independently of tumor growth. The multiple phenotypes regulated by IGF1R must be considered during development of this therapeutic strategy as inhibition of metastasis independent of inhibition of tumor growth is not easily assessed in phase II clinical trials. |
format | Text |
id | pubmed-2843625 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
record_format | MEDLINE/PubMed |
spelling | pubmed-28436252010-07-14 The type I insulin-like growth factor receptor regulates cancer metastasis independently of primary tumor growth by promoting invasion and survival Sachdev, Deepali Zhang, Xihong Matise, Ilze Gaillard-Kelly, Martine Yee, Douglas Oncogene Article The type I insulin-like growth factor receptor (IGF1R) regulates multiple aspects of malignancy and is the target of several drugs currently in clinical trials. While IGF1R’s role in proliferation and survival is well-studied, the regulation of metastasis by IGF1R is not as clearly delineated. Previous work showed that disruption of IGF1R signaling via overexpression of a dominant negative IGF1R inhibited metastasis. To establish a clinically applicable approach to inhibition of metastasis by targeting IGF1R, the effect of an inhibitory antibody against IGF1R, EM164 and its humanized version, AVE1642 on metastasis of cancer cells was examined. EM164 and AVE1642 did not affect primary tumor growth of MDA-435A/LCC6 cells but inhibited metastasis of these cells. Consistent with this inhibition in the formation of metastatic nodules, disruption of IGF1R also resulted in a decreased number of circulating tumor cells in blood of tumor-bearing mice. Disruption of IGF1R with a dominant negative construct or antibody inhibited invasion across Matrigel in vitro. When tumor cells were directly injected into the circulation via the lateral tail vein of mice, IGF1R disruption also resulted in significant reduction of pulmonary nodules, suggesting that regulation of invasion is not the only function of IGF1R signaling. Further, disruption of IGF1R rendered cells more susceptible to anoikis. Thus, IGF1R regulated metastasis independently of tumor growth. The multiple phenotypes regulated by IGF1R must be considered during development of this therapeutic strategy as inhibition of metastasis independent of inhibition of tumor growth is not easily assessed in phase II clinical trials. 2009-10-19 2010-01-14 /pmc/articles/PMC2843625/ /pubmed/19838209 http://dx.doi.org/10.1038/onc.2009.316 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Sachdev, Deepali Zhang, Xihong Matise, Ilze Gaillard-Kelly, Martine Yee, Douglas The type I insulin-like growth factor receptor regulates cancer metastasis independently of primary tumor growth by promoting invasion and survival |
title | The type I insulin-like growth factor receptor regulates cancer metastasis independently of primary tumor growth by promoting invasion and survival |
title_full | The type I insulin-like growth factor receptor regulates cancer metastasis independently of primary tumor growth by promoting invasion and survival |
title_fullStr | The type I insulin-like growth factor receptor regulates cancer metastasis independently of primary tumor growth by promoting invasion and survival |
title_full_unstemmed | The type I insulin-like growth factor receptor regulates cancer metastasis independently of primary tumor growth by promoting invasion and survival |
title_short | The type I insulin-like growth factor receptor regulates cancer metastasis independently of primary tumor growth by promoting invasion and survival |
title_sort | type i insulin-like growth factor receptor regulates cancer metastasis independently of primary tumor growth by promoting invasion and survival |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2843625/ https://www.ncbi.nlm.nih.gov/pubmed/19838209 http://dx.doi.org/10.1038/onc.2009.316 |
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