Extracellular nucleotides inhibit growth of human oesophageal cancer cells via P2Y2-receptors

Extracellular ATP is known to inhibit growth of various tumours by activating specific purinergic receptors (P2-receptors). Since the therapy of advanced oesophageal cancer is unsatisfying, new therapeutic approaches are mandatory. Here, we investigated the functional expression and potential antipr...

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Bibliographic Details
Published in:British journal of cancer 2002-02, Vol.86 (4), p.636-644
Main Authors: Maaser, K, Höpfner, M, Kap, H, Sutter, A P, Barthel, B, von Lampe, B, Zeitz, M, Scherübl, H
Format: Article
Language:English
Subjects:
Antineoplastic agents
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Cancer Research
Drug Resistance
Epidemiology
Experimental Therapeutics
General aspects
Medical sciences
Molecular Medicine
Oncology
Pharmacology. Drug treatments
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Summary:Extracellular ATP is known to inhibit growth of various tumours by activating specific purinergic receptors (P2-receptors). Since the therapy of advanced oesophageal cancer is unsatisfying, new therapeutic approaches are mandatory. Here, we investigated the functional expression and potential antiproliferative effects of P2-purinergic receptors in human oesophageal cancer cells. Prolonged incubation of primary cell cultures of human oesophageal cancers as well as of the squamous oesophageal cancer cell line Kyse-140 with ATP or its stable analogue ATPγS dose-dependently inhibited cell proliferation. This was due to both an induction of apoptosis and cell cycle arrest. The expression of P2-receptors was examined by RT-PCR, immunocytochemistry, and [Ca 2+ ] i -imaging. Application of various extracellular nucleotides dose-dependently increased [Ca 2+ ] i . The rank order of potency was ATP=UTP>ATPγS>ADP=UDP. 2-methylthio-ATP and α,β-methylene-ATP had no effects on [Ca 2+ ] i . Complete cross-desensitization between ATP and UTP was observed. Moreover, the phospholipase C inhibitor U73122 dose-dependently reduced the ATP triggered [Ca 2+ ] i signal. The pharmacological features strongly suggest the functional expression of G-protein coupled P2Y 2 -receptors in oesophageal squamous cancer cells. P2Y 2 -receptors are involved in the antiproliferative actions of extracellular nucleotides. Thus, P2Y 2 -receptors are promising target proteins for innovative approaches in oesophageal cancer therapy.
ISSN:0007-0920
1532-1827
DOI:10.1038/sj.bjc.6600100