Tumor suppressor KAI1 affects integrin {alpha}v{beta}3-mediated ovarian cancer cell adhesion, motility, and proliferation

Journal Article · Wed Jun 10 00:00:00 EDT 2009 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2009.01.007· OSTI ID:22209772

Ruseva, Zlatna; Geiger, Pamina Xenia Charlotte ^[1]; Hutzler, Peter ^[2]; Kotzsch, Matthias ^[3]; Luber, Birgit ^[2]; Schmitt, Manfred ^[1]; Gross, Eva ^[4]; Reuning, Ute ^[1]

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1. Clinical Research Unit, Department of Gynecology and Obstetrics, Technische Universitaet Muenchen Ismaninger Str. 22, D-81675 Munich (Germany)
2. Institute of Pathology, Technische Universitaet Muenchen (Germany)
3. Institute of Pathology, Technische Universitaet Dresden (Germany)
4. Gynecol. Tumor Genetics, Department of Gynecology and Obstetrics, Technische Universitaet Muenchen (Germany)

The tetraspanin KAI1 had been described as a metastasis suppressor in many different cancer types, a function for which associations of KAI1 with adhesion and signaling receptors of the integrin superfamily likely play a role. In ovarian cancer, integrin {alpha}v{beta}3 correlates with tumor progression and its elevation in vitro provoked enhanced cell adhesion accompanied by significant increases in cell motility and proliferation in the presence of its major ligand vitronectin. In the present study, we characterized integrin {alpha}v{beta}3-mediated tumor biological effects as a function of cellular KAI1 restoration and proved for the first time that KAI1, besides its already known physical crosstalk with {beta}1-integrins, also colocalizes with integrin {alpha}v{beta}3. Functionally, elevated KAI1 levels drastically increased integrin {alpha}v{beta}3/vitronectin-dependent ovarian cancer cell adhesion. Since an intermediate level of cell adhesive strength is required for optimal cell migration, we next studied ovarian cancer cell motility as a function of KAI1 restoration. By time lapse video microscopy, we found impaired integrin {alpha}v{beta}3/vitronectin-mediated cell migration most probably due to strongly enhanced cellular immobilization onto the adhesion-supporting matrix. Moreover, KAI1 reexpression significantly diminished cell proliferation. These data strongly indicate that KAI1 may suppress ovarian cancer progression by inhibiting integrin {alpha}v{beta}3/vitronectin-provoked tumor cell motility and proliferation as important hallmarks of the oncogenic process.

• OSTI ID: 22209772
• Journal Information: Experimental Cell Research, Vol. 315, Issue 10; Other Information: Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BIOLOGICAL EFFECTS
CELL PROLIFERATION
IN VITRO
METASTASES
MICROSCOPY
NEOPLASMS
RECEPTORS
TUMOR CELLS