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Pentoxifylline modulates cell surface integrin expression and integrin mediated adhesion of B16F10 cells to extracellular matrix components
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Ratheesh, Aparna, Ingle, Arvind and Gude, Rajiv P. (2007) Pentoxifylline modulates cell surface integrin expression and integrin mediated adhesion of B16F10 cells to extracellular matrix components. Cancer Biology & Therapy, 6 (11). pp. 1743-1752. doi:10.4161/cbt.6.11.4833 ISSN 1538-4047.
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Official URL: http://dx.doi.org/10.4161/cbt.6.11.4833
Abstract
Our previous studies demonstrated that Pentoxifylline (PTX), a phosphodiesterase inhibitor could inhibit the lung homing of B16-F10 melanoma cells in C57BL/6 mice. In this study we have looked at the effect of PTX on cell surface integrin expression and integrin mediated adhesion of B16-F10 melanoma cells. B16F10 cells treated with PTX when injected through the tail vein of mice showed a 75% reduction in pulmonary nodules as compared to control untreated cells. PTX brought about a significant reduction in the integrin mediated adhesion of F10 cells to Fibronectin and Vitronectin (58.75% + 3.4 S.E and 60% + 1.7 S.E respectively if control was considered as 100 %). This inhibition in adhesion was evident upto 4 hours only and treatment for 24 hours brought about an increase in adhesion (135.5 % + 0.5 S.E). Flow cytometric analysis showed higher surface expressions of αv, α5 and αIIb integrin subunits in B16-F10 as compared to the low metastatic cell line B16-F1 suggesting a role for these integrins in determining the metastatic potential. PTX brought about a significant decrease in the cell surface expression of α5, αIIb and β1integrin subunits but not that of the αv subunit on B16-F10 cells. PTX also brought about a reduction in the total cellular protein levels of β1 and αv integrin subunits. Various isoforms of Protein Kinase C (PKC) has been shown to regulate integrin expression, localization and activity. Hence we looked at the effect of PTX on total cellular PKC activity. PTX brought about a significant reduction in total cellular PKC activity (82.66 + 0.593). Collectively our results indicate that the antimetastatic action of PTX is mediated, at least in part through its effects on adhesion and the surface expression of specific integrin receptors.
Item Type: | Journal Article | ||||||
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Journal or Publication Title: | Cancer Biology & Therapy | ||||||
Publisher: | Taylor & Francis Inc. | ||||||
ISSN: | 1538-4047 | ||||||
Official Date: | 2007 | ||||||
Dates: |
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Volume: | 6 | ||||||
Number: | 11 | ||||||
Page Range: | pp. 1743-1752 | ||||||
DOI: | 10.4161/cbt.6.11.4833 | ||||||
Status: | Peer Reviewed | ||||||
Publication Status: | Published | ||||||
Access rights to Published version: | Restricted or Subscription Access |
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