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

Abstract

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 ATPgS dose-dependently inhibited cell proliferation. This was due to both an induction of apoptosis and cell cycle arrest.

Purinergic receptor‐mediated effects of ATP in high‐grade bladder cancer

“…UTP caused an overall increase in the number of viable cells, which is contrary to the findings of other groups investigating oesophageal and colon cancer [11,12], but concordant with the recognized growthstimulatory effects of P2Y receptor subtypes as previously described [14].…”

“…The present data suggest that the antineoplastic action of ATP is mediated via P2X 5 receptors, although the exact role of the P2Y 11 receptor cannot be defined due to the paucity of effective selective agonists and antagonists for this receptor subtype. This receptor profile is the same as that previously reported in the hormone-refractory prostatic cancer cell lines PC-3 and DU145 [7] although the bladder cancer cells were significantly more sensitive to the effects of ATP.…”

“…Extracellular nucleotides, such as ATP, have previously been shown to be involved in the control of cell growth in various malignancies including oesophageal [11], colon [12], ovarian [13] and hormone-refractory prostate cancers [7]. This trophic response has been found to be mediated via P2 receptor subtypes.…”

“…ATP acts via specific P2 receptor subtypes, P2X ionotropic (P2X [1][2][3][4][5][6][7] ) and P2Y metabotropic (P2Y 1,2,4,6,11,12,13,14 ), and can induce trophic responses in various cells that include cell proliferation, cell differentiation, and cell death [6]. It has been shown that purinergic agonists are able to inhibit the growth of poorly differentiated hormone-refractory prostate adenocarcinoma cells in vitro via P2 receptor-mediated apoptosis [7].…”

ATP reduces gel compaction in osteoblast-populated collagen gels

“…Since bone remodeling is a localized process (3), the local extracellular ATP may play a critical role in bone remodeling by converting the broad, systemic mechanical stimuli into local signals. Extracellular ATP, released from cells by lytic or nonlytic mechanisms, plays a number of diverse roles in vivo and in vitro, such as membrane permeability (27), induction of apoptosis (44), organic anion transport (such as bilirubin) (5), calcium mobilization (12), cell proliferation (38), contractility (34), wound healing (8), excitation of sympathetic neurons (25), inhibition of tumors (28), and bone remodeling (3). ATP interacts with P2 receptors that have been divided into two subfamilies: P2X (ligand-gated cation channels) and P2Y (G protein-coupled receptors) (23).…”