Insulin-Like Growth Factor-II Bound to Vitronectin Enhances MCF-7 Breast Cancer Cell Migration

We have previously reported that IGF-II binds the extracellular matrix protein vitronectin (VN) with an affinity similar to that for the type-1 IGF receptor (IGF-1R). In view of this finding, and given the cited role of VN in cell motility and adhesion, we aimed to elucidate the functional consequen...

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Bibliographic Details
Published in:Endocrinology (Philadelphia) 2003-06, Vol.144 (6), p.2417-2424
Main Authors: Noble, Anthony, Towne, Chris, Chopin, Lisa, Leavesley, David, Upton, Zee
Format: Article
Language:English
Subjects:
Affinity
Binding
Biological and medical sciences
Breast cancer
Breast carcinoma
Breast Neoplasms
Cell adhesion
Cell adhesion & migration
Cell Adhesion - drug effects
Cell Adhesion - physiology
Cell migration
Cell Movement - drug effects
Cell Movement - physiology
Extracellular matrix
Fundamental and applied biological sciences. Psychology
Growth factors
Humans
In Vitro Techniques
Insulin-like growth factor I receptors
Insulin-like growth factor II
Insulin-Like Growth Factor II - analogs & derivatives
Insulin-Like Growth Factor II - metabolism
Insulin-Like Growth Factor II - pharmacology
Insulin-like growth factors
Matrix protein
Protein biosynthesis
Protein synthesis
Proteins
Tumor Cells, Cultured
Vitronectin
Vitronectin - metabolism
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Summary:We have previously reported that IGF-II binds the extracellular matrix protein vitronectin (VN) with an affinity similar to that for the type-1 IGF receptor (IGF-1R). In view of this finding, and given the cited role of VN in cell motility and adhesion, we aimed to elucidate the functional consequences of this interaction on cellular processes relevant to breast carcinoma. We demonstrate that this complex slightly inhibits cell attachment and has little effect on protein synthesis in MCF-7 breast cancer cells. However, prebinding IGF-II to immobilized VN was found to significantly enhance breast cancer cell migration through Transwells. Interestingly, IGF-II bound to VN, and not IGF-II in solution in the presence of VN, seems to be responsible for the effects on cell migration. Furthermore, studies using analogs of IGF-II with reduced affinity for the IGF-1R or IGF binding proteins indicate that this response involves the IGF-1R but is independent of IGF binding proteins. This is the first study demonstrating that IGF-II:VN complexes enhance migration of cells. This may prove to be especially relevant, given that overexpression of IGF-II and VN are features of many tumors.
ISSN:0013-7227
1945-7170
DOI:10.1210/en.2002-221138