This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Muthukumaran, N. Articles by Rodríguez-Rodríguez, L. Search for Related Content PubMed PubMed Citation Articles by Muthukumaran, N. Articles by Rodríguez-Rodríguez, L.

---

Angiogenesis, Metastasis, and the Cellular Microenvironment

Tumor Necrosis Factor- Differentially Modulates CD44 Expression in Ovarian Cancer Cells

¹ Department of Obstetrics and Gynecology and Reproductive Sciences, and ² Division of Gynecologic Oncology, The Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey

Requests for reprints: Lorna Rodríguez-Rodríguez, Division of Gynecologic Oncology, The Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Room 2009, 195 Little Albany Street, New Brunswick, NJ 08901. Fax: 732-235-9831. E-mail: rodriglo{at}umdnj.edu

Chronic inflammation is implicated in the pathophysiology of ovarian cancer. Tumor necrosis factor- (TNF-), a major inflammatory cytokine, is abundant in the ovarian cancer microenvironment. TNF- modulates the expression of CD44 in normal T lymphocytes and CD44 is implicated in ovarian carcinogenesis and metastases. However, little is known about the role of TNF- in CD44 expression of cancer cells. Recent clinical work using TNF- inhibitors for the treatment of ovarian cancer makes the study of TNF- interactions with CD44 crucial to determining treatment a success or a failure. We studied the effect of TNF- on ovarian cancer cells viability, CD44 expression, and in vitro migration/invasion. Our results revealed that TNF- differentially modulates the expression of CD44 in TNF--resistant ovarian cancer cells, affecting their in vitro migration, invasion, and binding to hyaluronic acid. TNF- up-regulation of CD44 expression was dependent on the activation of c-Jun NH₂-terminal kinase (JNK) and this activation was accompanied by an increase in their invasive phenotype. On the contrary, if TNF- failed to induce JNK phosphorylation, the end result was down-regulation of both CD44 expression and the invasive phenotype. These results were confirmed by the use of JNK inhibitors and a TNF receptor competitive inhibitor. (Mol Cancer Res 2006;4(8):511–20)

This article has been cited by other articles:

				C. M. Annunziata, L. Kleinberg, B. Davidson, A. Berner, D. Gius, N. Tchabo, S. M. Steinberg, and E. C. Kohn BAG-4/SODD and Associated Antiapoptotic Proteins Are Linked to Aggressiveness of Epithelial Ovarian Cancer Clin. Cancer Res., November 15, 2007; 13(22): 6585 - 6592. [Abstract] [Full Text] [PDF]