Downregulation of connective tissue growth factor by three-dimensional matrix enhances ovarian carcinoma cell invasion

Maria V. Barbolina, Brian P. Adley, David L. Kelly, Jaclyn Shepard, Angela J. Fought, Denise Scholtens, Peter Penzes, Lonnie D. Shea, M. Sharon Stack

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Epithelial ovarian carcinoma (EOC) is a leading cause of death from gynecologic malignancies, due mainly to the prevalence of undetected metastatic disease. The process of cell invasion during intraperitoneal anchoring of metastatic lesions requires concerted regulation of many processes, including modulation of adhesion to the extracellular matrix and localized invasion. Exploratory cDNA microarray analysis of early response genes (altered after 4 hr of 3D collagen culture) coupled with confirmatory real-time reverse-transcriptase polymerase chain reaction, multiple 3D cell culture matrices, Western blot, immunostaining, adhesion, migration and invasion assays were used to identify modulators of adhesion pertinent to EOC progression and metastasis. cDNA microarray analysis indicated a dramatic downregulation of connective tissue growth factor (CTGF) in EOC cells placed in invasionmimicking conditions (3D Type I collagen). Examination of human EOC specimens revealed that CTGF expression was absent in 46% of the tested samples (n = 41), but was present in 100% of normal ovarian epithelium samples (n = 7). Reduced CTGF expression occurs in many types of cells and may be a general phenomenon displayed by cells encountering a 3D environment. CTGF levels were inversely correlated with invasion such that downregulation of CTGF increased, while its upregulation reduced collagen invasion. Cells adhered preferentially to a surface comprised of both collagen I and CTGF relative to either component alone using α6β1 and α3β1 integrins. Together these data suggest that downregulation of CTGF in EOC cells may be important for cell invasion through modulation of cell-matrix adhesion.

Original languageEnglish (US)
Pages (from-to)816-825
Number of pages10
JournalInternational Journal of Cancer
Volume125
Issue number4
DOIs
StatePublished - Aug 15 2009

Keywords

  • Adhesion
  • Connective tissue growth factor
  • Invasion
  • Metastasis
  • Ovarian carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Downregulation of connective tissue growth factor by three-dimensional matrix enhances ovarian carcinoma cell invasion'. Together they form a unique fingerprint.

  • Cite this

    Barbolina, M. V., Adley, B. P., Kelly, D. L., Shepard, J., Fought, A. J., Scholtens, D., Penzes, P., Shea, L. D., & Stack, M. S. (2009). Downregulation of connective tissue growth factor by three-dimensional matrix enhances ovarian carcinoma cell invasion. International Journal of Cancer, 125(4), 816-825. https://doi.org/10.1002/ijc.24347