Laminin binding integrins 6 (CD49f) and 3 (CD49c) are persistently but differentially expressed in prostate cancer (PCa). Integrin internalization is an important determinant of their cell surface expression and function. Using flow cytometry, and first order kinetic modeling, we quantitated the intrinsic internalization rates of integrin subunits in a single cycle of internalization. In PCa cell line DU145, 6 integrin internalized with a rate constant (k(actual)) of 3.25min(-1), threefold faster than 3 integrin (1.0min(-1)), 1.5-fold faster than the vitronectin binding v integrin (CD51) (2.2min(-1)), and significantly slower than the unrelated transferrin receptor (CD71) (15min(-1)). Silencing of 3 integrin protein expression in DU145, PC3, and PC3B1 cells resulted in up to a 1.71-fold increase in k(actual) for 6 integrin. The internalized 6 integrin was targeted to early endosomes but not to lamp1 vesicles. Depletion of 3 integrin expression resulted in redistribution of 64 integrin to an observed cell-cell staining pattern that is consistent with a suprabasal distribution observed in epidermis and early PIN lesions in PCa. Depletion of 3 integrin increased cell migration by 1.8-fold, which was dependent on 61 integrin. Silencing of 6 integrin expression however, had no significant effect on the k(actual) of 3 integrin or its distribution in early endosomes. These results indicate that 3 and 6 integrins have significantly different internalization kinetics and that coordination exists between them for internalization. J. Cell. Biochem. 118: 1038-1049, 2017.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/623537 |
| Date | 05 1900 |
| Creators | Das, Lipsa, Anderson, Todd A., Gard, Jaime M.C., Sroka, Isis C., Strautman, Stephanie R., Nagle, Raymond B., Morrissey, Colm, Knudsen, Beatrice S., Cress, Anne E. |
| Contributors | Cancer Biology Program, University of Arizona, he University of Arizona Cancer Center, University of Arizona, Department of Pharmacology, University of Arizona, Tucson, Department of Molecular and Cellular Biology, University of Arizona, Department of Pathology, University of Arizona, Department of Cellular and Molecular Medicine, University of Arizona, Cancer Biology Program; University of Arizona; Tucson Arizona 85724, The University of Arizona Cancer Center, University of Arizona; Tucson Arizona 85724, The University of Arizona Cancer Center, University of Arizona; Tucson Arizona 85724, Department of Pharmacology; University of Arizona; Tucson Arizona 85724, Department of Molecular and Cellular Biology; University of Arizona; Tucson Arizona 85724, The University of Arizona Cancer Center, University of Arizona; Tucson Arizona 85724, University of Washington; Seattle Washington 98195, Cedars Sinai Medical Center; Los Angeles California 90048, The University of Arizona Cancer Center, University of Arizona; Tucson Arizona 85724 |
| Publisher | WILEY |
| Source Sets | University of Arizona |
| Language | English |
| Detected Language | English |
| Type | Article |
| Rights | © 2016 Wiley Periodicals, Inc. |
| Relation | http://doi.wiley.com/10.1002/jcb.25673 |
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