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Research Paper
A Naturally Occurring Truncated β3 Integrin in Tumor Cells: Native Anti-integrin Involved in Tumor Cell Motility
Rongxian Jin, Mohit Trikha, Yinlong Cai, David Grignon and Kenneth V. Honn
volume 6 | issue 10
October 2007Pages: 1559 - 1568
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Alternatively spliced integrins may play an important role in integrin mediated tumor cell adhesion, spreading, and migration. Here we report in human tumor cells a naturally occurring alternatively spliced variant of the β3 integrin [i.e. truncated (tr) β3] that lacked a cytoplasmic and a transmembrane domain. The presence of tr-β3 was demonstrated at the mRNA level by RT-PCR, cloning, and sequencing; at the protein level by immunohistochemistry and Western Blotting. The alternately spliced β3 integrin was detected in human prostate carcinomas, breast carcinomas, and melanoma cells. Expression in vivo was confirmed by immunohistochemistry with an antibody to tr-β3 that does not recognize wild type β3. Tumor cells secreted this protein and deposited it on the extracellular matrix. Secreted tr-β3 inhibited adhesion of melanoma and prostate cancer cells to fibronectin and vitronectin, which was partially reversed by adsorption of tr-β3 from the media. Confocal microscopy and time lapse live cell microscopy demonstrated that tr-β3 distributed to the trailing edge of migrating cells, which may represent an alternative cell detachment mechanism in these cells. Results suggest that tr-β3 may act as an anti-integrin and play a crucial role in cell migration, which is an important process in tumor invasion and metastasis.
Authors
Rongxian Jin
Department of Radiation Oncology, Wayne State University, Detroit, MI
Mohit Trikha
Department of Radiation Oncology, Wayne State University, Detroit, MI
Yinlong Cai
Department of Radiation Oncology, Wayne State University, Detroit, MI
David Grignon
Department of Pathology, Wayne State University, Detroit, MI
Kenneth V. Honn
Departments of Radiation Oncology, Pathology and Chemistry, Wayne State University, Detroit, MI; 5Barbara Ann Karmanos Cancer Center, The Detroit Medical Center, Detroit, MI
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.