PMID- 16908592 OWN - NLM STAT- MEDLINE DCOM- 20061012 LR - 20171116 IS - 1541-7786 (Print) IS - 1541-7786 (Linking) VI - 4 IP - 8 DP - 2006 Aug TI - Tumor necrosis factor-alpha differentially modulates CD44 expression in ovarian cancer cells. PG - 511-20 AB - Chronic inflammation is implicated in the pathophysiology of ovarian cancer. Tumor necrosis factor-alpha (TNF-alpha), a major inflammatory cytokine, is abundant in the ovarian cancer microenvironment. TNF-alpha 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-alpha in CD44 expression of cancer cells. Recent clinical work using TNF-alpha inhibitors for the treatment of ovarian cancer makes the study of TNF-alpha interactions with CD44 crucial to determining treatment a success or a failure. We studied the effect of TNF-alpha on ovarian cancer cells viability, CD44 expression, and in vitro migration/invasion. Our results revealed that TNF-alpha differentially modulates the expression of CD44 in TNF-alpha-resistant ovarian cancer cells, affecting their in vitro migration, invasion, and binding to hyaluronic acid. TNF-alpha up-regulation of CD44 expression was dependent on the activation of c-Jun NH(2)-terminal kinase (JNK) and this activation was accompanied by an increase in their invasive phenotype. On the contrary, if TNF-alpha 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. FAU - Muthukumaran, Neelakandan AU - Muthukumaran N AD - 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, 08901, USA. FAU - Miletti-Gonzalez, Karl E AU - Miletti-Gonzalez KE FAU - Ravindranath, Abhilash K AU - Ravindranath AK FAU - Rodriguez-Rodriguez, Lorna AU - Rodriguez-Rodriguez L LA - eng GR - CA66077/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Mol Cancer Res JT - Molecular cancer research : MCR JID - 101150042 RN - 0 (CD44 protein, human) RN - 0 (Drug Combinations) RN - 0 (Hyaluronan Receptors) RN - 0 (Laminin) RN - 0 (Proteoglycans) RN - 0 (Tumor Necrosis Factor-alpha) RN - 119978-18-6 (matrigel) RN - 9004-61-9 (Hyaluronic Acid) RN - 9007-34-5 (Collagen) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM MH - Cell Proliferation/drug effects MH - Cell Survival/drug effects MH - Collagen/drug effects MH - Drug Combinations MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Female MH - Gene Expression Regulation, Neoplastic/*drug effects MH - Humans MH - Hyaluronan Receptors/*metabolism MH - Hyaluronic Acid/metabolism MH - Laminin/drug effects MH - Neoplasm Invasiveness MH - Ovarian Neoplasms/*metabolism MH - Proteoglycans/drug effects MH - Tumor Cells, Cultured MH - Tumor Necrosis Factor-alpha/metabolism/*pharmacology EDAT- 2006/08/16 09:00 MHDA- 2006/10/13 09:00 CRDT- 2006/08/16 09:00 PHST- 2006/08/16 09:00 [pubmed] PHST- 2006/10/13 09:00 [medline] PHST- 2006/08/16 09:00 [entrez] AID - 4/8/511 [pii] AID - 10.1158/1541-7786.MCR-05-0232 [doi] PST - ppublish SO - Mol Cancer Res. 2006 Aug;4(8):511-20. doi: 10.1158/1541-7786.MCR-05-0232.