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

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

Research output: Contribution to journalArticle

32 Citations (Scopus)

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

Fingerprint

Connective Tissue Growth Factor
Down-Regulation
Carcinoma
Collagen
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Cell-Matrix Junctions
Collagen Type I
Reverse Transcriptase Polymerase Chain Reaction
Integrins
Extracellular Matrix
Real-Time Polymerase Chain Reaction
Cause of Death
Up-Regulation
Epithelium
Cell Culture Techniques
Western Blotting
Neoplasm Metastasis

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Downregulation of connective tissue growth factor by three-dimensional matrix enhances ovarian carcinoma cell invasion. / Barbolina, Maria V.; Adley, Brian P.; Kelly, David Lee; Shepard, Jaclyn; Fought, Angela J.; Scholtens, Denise; Penzes, Peter; Shea, Lonnie D.; Stack, M. Sharon.

In: International Journal of Cancer, Vol. 125, No. 4, 15.08.2009, p. 816-825.

Research output: Contribution to journalArticle

Barbolina, MV, Adley, BP, Kelly, DL, Shepard, J, Fought, AJ, Scholtens, D, Penzes, P, Shea, LD & Stack, MS 2009, 'Downregulation of connective tissue growth factor by three-dimensional matrix enhances ovarian carcinoma cell invasion', International Journal of Cancer, vol. 125, no. 4, pp. 816-825. https://doi.org/10.1002/ijc.24347
Barbolina, Maria V. ; Adley, Brian P. ; Kelly, David Lee ; Shepard, Jaclyn ; Fought, Angela J. ; Scholtens, Denise ; Penzes, Peter ; Shea, Lonnie D. ; Stack, M. Sharon. / Downregulation of connective tissue growth factor by three-dimensional matrix enhances ovarian carcinoma cell invasion. In: International Journal of Cancer. 2009 ; Vol. 125, No. 4. pp. 816-825.
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