Altered in vitro spreading and cytoskeletal organization in human glioma cells by downregulation of urokinase receptor

Shravan K. Chintala, Sanjeeva Mohanam, Yoshinori Go, Boyapati Venkaiah, Raymond Sawaya, Ziya L. Gokaslan, Jasti S. Rao

Research output: Contribution to journalArticlepeer-review

Abstract

The interaction of urokinase-type plasminogen activator (uPA) with its cell-surface receptor (uPAR) is implicated in diverse biological processes such as cell migration, tissue remodeling, and tumor cell invasion. Recent studies indicated that uPAR can act as an extracellular matrix receptor during cell adhesion. Recently, we showed that transfection of the human glioma cell line SNB19 with antisense uPAR resulted in downregulation of uPAR at both the mRNA and protein levels. In this study, we used SNB19 to determine how the presence or absence of uPAR promotes cell spreading and associated changes in cell morphology. Microscopic analysis of cell spreading revealed that antisense uPAR-transfected cells were larger, remained round, and did not spread efficiently over extracellular matrix substrate type IV collagen and fibronectin, unlike parental SNB19 cells, which were smaller and spindle shaped. Biochemical studies showed that antisense uPAR-transfected cells, in addition to not spreading, exhibited increased expression of α3β1 integrin but not α5β1 integrin. However, we could not find a change in the expression of extracellular matrix components or altered growth rate in these cells. Furthermore, despite the increased α3β1 integrin expression, antisense uPAR-transfected cells failed to form an organized actin cytoskeleton when plated on type IV collagen or fibronectin, unlike parental SNB19 cells, which displayed an organized cytoskeleton. These findings show that the absence of uPAR in human glioma cells leads to morphological changes associated with decreased spreading and a disorganized cytoskeleton resulting in altered cell morphology, suggesting that coordinated expression of uPAR and integrin may be involved in spreading of antisense uPAR-transfected glioma cells.

Original languageEnglish (US)
Pages (from-to)355-365
Number of pages11
JournalMolecular Carcinogenesis
Volume20
Issue number4
DOIs
StatePublished - Dec 1997

Keywords

  • Adhesion
  • Glioblastoma
  • Invasion
  • Plasminogen activators
  • Spreading
  • Urokinase-type plasminogen activator receptor

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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