Wound-induced migration of MDA-MB-435 and SKOV-3 cancer cells is regulated by plasminogen activator inhibitor-1

  • Authors:
    • Brandi R. Whitley
    • Frank C. Church
  • View Affiliations

  • Published online on: September 1, 2005     https://doi.org/10.3892/ijo.27.3.749
  • Pages: 749-757
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Abstract

Plasminogen activator inhibitor-1 (PAI-1) regulates the proteolytic activity of urokinase-type plasminogen activator (uPA) and there is increasing evidence for a PAI-1 role in regulating cell migration/invasion by other mechanisms like vitronectin (VN) binding and lipoprotein-receptor related protein (LRP) binding. We examined the role of PAI-1 to interact with uPA, VN, and LRP in MDA-MB-435 breast cancer and SKOV-3 ovarian cancer cells in a wound-induced cell migration assay. By different experimental conditions with PAI-1, expressed either by stable transfection or by adenoviral infection (wild-type PAI-1 and an inactive reactive site P14 mutant, T333R) or by addition of recombinant PAI-1 and various mutants (stable wild-type, P14 T333R, reactive center P1 R346A, reduced VN-binding Q123K, and reduced LRP-binding R76E), we found that the PAI-1-VN interaction was foremost in suppressing wound-induced cell migration. Likewise, a VN-antibody that blocks cell adhesion to VN mimicked the effect of PAI-1 to reduce wound-induced SKOV-3 cell migration. However, manipulation of the endogenous plasminogen activator system (using blocking antibodies to PAI-1 and to uPA) in wound-induced SKOV-3 cell migration demonstrated an important role for uPA inhibition by PAI-1 that was dependent on plasminogen. By contrast, smooth muscle cell wound-induced migration was promoted by exogenously added PAI-1, but this enhancement was dependent on PAI-1 binding to LRP, not binding to VN. These findings contribute to the overall complexity of the role of PAI-1 in regulating cell migration; especially since both VN binding and uPA inhibition are involved in suppressing wound-induced breast and ovarian cancer cell migration.

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September 2005
Volume 27 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Whitley BR and Whitley BR: Wound-induced migration of MDA-MB-435 and SKOV-3 cancer cells is regulated by plasminogen activator inhibitor-1. Int J Oncol 27: 749-757, 2005
APA
Whitley, B.R., & Whitley, B.R. (2005). Wound-induced migration of MDA-MB-435 and SKOV-3 cancer cells is regulated by plasminogen activator inhibitor-1. International Journal of Oncology, 27, 749-757. https://doi.org/10.3892/ijo.27.3.749
MLA
Whitley, B. R., Church, F. C."Wound-induced migration of MDA-MB-435 and SKOV-3 cancer cells is regulated by plasminogen activator inhibitor-1". International Journal of Oncology 27.3 (2005): 749-757.
Chicago
Whitley, B. R., Church, F. C."Wound-induced migration of MDA-MB-435 and SKOV-3 cancer cells is regulated by plasminogen activator inhibitor-1". International Journal of Oncology 27, no. 3 (2005): 749-757. https://doi.org/10.3892/ijo.27.3.749