1. ¹Department of Chemical and Biochemical Engineering, Northwestern University, Chicago, IL, USA
2. ²Department of Pathology, Northwestern University, Chicago, IL, USA
3. ³Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA
4. ⁴Department of Preventive Medicine, Northwestern University, Chicago, IL, USA
5. ⁵Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO, USA

Correspondence: Dr M Sharon Stack, PhD, Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, One Hospital Drive, M214E Medical Sciences Building, Columbia, MO, 65212, USA. E-mail: stackm@health.missouri.edu

Received 20 November 2007; Revised 21 January 2008; Accepted 22 January 2008; Published online 24 March 2008.

Abstract

Advanced and metastatic ovarian cancer is a leading cause of death from gynecologic malignancies. A more detailed understanding of the factors controlling invasion and metastasis may lead to novel anti-metastatic therapies. To model cellular interactions that occur during intraperitoneal metastasis, comparative cDNA microarray analysis and confirmatory real-time reverse transcription PCR (RT-PCR) were employed to uncover changes in gene expression that may occur in late stage ovarian cancer in response to microenvironmental cues, particularly native three-dimensional collagen I. Gene expression in human ovarian carcinoma tissues was evaluated on the RNA and protein level using real-time RT-PCR and immunohistochemistry. Cell invasion and migration were evaluated in a collagen invasion assay and a scratch wound assay. Three-dimensional collagen I culture led to differential expression of several genes. The role of actinin alpha-4 (ACTN4), a cytoskeleton-associated protein implicated in the regulation of cell motility, was examined in detail. ACTN4 RNA and protein expression were associated with advanced and metastatic human ovarian carcinoma. This report demonstrates that a cytoskeletal-associated protein ACTN4 is upregulated by three-dimensional collagen culture conditions, leading to increased invasion and motility of ovarian cancer cells. Expression of ACTN4 in human ovarian tumors was found to be associated with advanced-stage disease and peritoneal metastases.