Details

Autor(en) / Beteiligte

• Schulte, Klaus‐Martin
• Beyer, Andreas
• Köhrer, Karl
• Oberhäuser, Simone
• Röher, Hans‐Dietrich

Titel

Lysophosphatidic acid, a novel lipid growth factor for human thyroid cells: Over‐expression of the high‐affinity receptor edg4 in differentiated thyroid cancer

Ist Teil von

• International journal of cancer, 2001-04, Vol.92 (2), p.249-256

Ort / Verlag

New York: John Wiley & Sons, Inc

Erscheinungsjahr

2001

Link zum Volltext

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• Lysophosphatidic acid (LPA) is a small lipid mediator with pleiotropic biological activities, e.g., the regulation of cellular proliferation and various aspects of cellular physiology. Signal transduction is achieved by binding to 2 high‐affinity receptors, EDG2 and EDG4, and a group of low‐affinity receptors, EDG1–7, all belonging to the superfamily of G protein–coupled receptors. We examined the growth‐regulatory effects of LPA in primary cultures of 8 goiters and 1 papillary thyroid cancer. We further assessed mRNA expression of high‐affinity receptors EDG2 and EDG4 in 14 normal thyroids, 29 papillary thyroid cancers, 7 follicular thyroid cancers and 13 goiters by quantitative RT‐PCR. We also identified mRNA expression of phospholipase A2 and LPA acyltransferase in fresh thyroid tissues derived from various sources. At concentrations of 10, 50 and 150 μM, LPA induced a 2‐fold rise of proliferation (p < 0.001) and acted as strongly as thyrotropin. The combination of LPA and TSH produced significant synergistic effects compared with each substance alone (p < 0.05). Normal thyroid, goiter and papillary or follicular thyroid cancer expressed 2 high‐affinity cognate LPA receptors, EDG2 and EDG4. EDG4 receptor mRNA expression was increased 3‐fold in differentiated thyroid cancer (p < 0.01), both papillary (p < 0.01) and follicular (p < 0.05), compared to normal thyroid or goiter. Overall expression of EDG2 receptor was unchanged in malignancy; however, increased EDG2 expression in individual samples correlated with lymphonodular metastasis (p = 0.01). Thus, lipid mediators are a novel class of factors involved in the control of proliferation in the human thyroid. Altered mRNA expression of the high‐affinity LPA receptor EDG4 suggests a role in the pathogenesis of differentiated thyroid cancer. © 2001 Wiley‐Liss, Inc.