Oxytocin synthesis and oxytocin receptor expression by cell lines of human small cell carcinoma of the lung stimulate tumor growth through autocrine/paracrine signaling
[en] The objective of the present work was to investigate the existence of an oxytocin (OT)-mediated autocrine/paracrine signaling upon small cell carcinoma of the lung (SCCL) cell growth. In that view, OT receptor (OTR) expression, concomitant with OT synthesis and secretion, was evidenced on three different SCCL cell lines (DMS79, H146, and H345) and related to the vasopressin (VP) system. Specific OT, VP, OTR, Via VP receptor (V1aR), and V1b/V3 VP receptor (V1bR/V3R) transcripts were identified by reverse transcription-.PCR in all cell lines studied. Binding of I-125-(d(CH2)(5)(1),Tyr(Me)(2), Thr(4), Orn(3),Tyr(9)-NH2)-vasotocin (OVTA) was observed on all SCCL cell lines, with a K-d (dissociation constant) ranging from 0.025-0.089 nm, depending; on the cell line and the analytical method. Selectivity of I-125-OVTA binding was confirmed by displacement curves obtained with various OTR and VP receptor agonists and antagonists (OT, OVTA, L-371,257, VP, F180). Immunocytochemistry identified cellular OT and VP, and peptide secretion was measured in supernatants of SCCL cultures. [H-3]Thymidine incorporations, applied on H345 cells, demonstrated a dose-dependent mitogenic effect of exogenous OT (1 and 100 nM) that was abolished by the OTR antagonist OVTA. A decrease of proliferation was also observed with OVTA alone, showing a functional mitogenic effect of tumor-derived OT. Taken together, these observations demonstrate the existence of a functional OT-mediated autocrine/paracrine signaling actively implicated in growth and development of SCCL tumors. Furthermore, these findings point to the potential of OT antagonists for development as therapeutic agents for the treatment of SCCL.
Disciplines :
Oncology
Author, co-author :
Pequeux, Christel ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Martens, Henri ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Embryologie
Winkler, Rose ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Geenen, Vincent ; Université de Liège - ULiège > Centre d'immunologie
Legros, Jean-Jacques ; Université de Liège - ULiège > Département des sciences cliniques > Département des sciences cliniques
Language :
English
Title :
Oxytocin synthesis and oxytocin receptor expression by cell lines of human small cell carcinoma of the lung stimulate tumor growth through autocrine/paracrine signaling
Publication date :
15 August 2002
Journal title :
Cancer Research
ISSN :
0008-5472
eISSN :
1538-7445
Publisher :
American Association for Cancer Research (AACR), Birmingham, United States - Maryland
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