Impairment of ATP-induced Ca2+ -signalling in human thyroid cancer cells.
Extracellular nucleotides like ATP that activate the Ca2+ -phosphatidylinositol (PI) signalling pathway have been suggested to participate in the regulation of normal human thyroid function. We examined, whether P2y-purinergic receptors are expressed on human thyroid cancer cells and whether post-receptor Ca2+ signalling is altered by malignant transformation. Extracellular ATP caused a biphasic increase in cytosolic free Ca2+ ([Ca2+]i) in normal human thyrocytes and in human follicular (FTC) and papillary (PTC) thyroid carcinoma cells. In FTC and PTC cell lines the dose-response curves for ATP-induced changes in [Ca2+]i were shifted to the right when compared with normal thyrocytes, whereas in undifferentiated thyroid carcinoma (UTC) cells even high concentrations of ATP (500 microM) failed to stimulate a rise in [Ca2+]i. By contrast, ATP stimulated inositol 1,4,5-trisphosphate (IP3) formation and capacitative Ca2+ entry was operational as judged by thapsigargin in normal thyrocytes and all thyroid cancer cells. Thus, P2y-purinergic receptors are expressed on thyroid tumor cells independent of degree of differentiation. In UTC cells, however, impairment in the Ca2+ -phosphatidylinositol (PI) signalling cascade occurs distal to the formation of IP3 and proximal to the activation of capacitative Ca2+ entry. Disturbed ATP-induced Ca2+ -signalling and alterations in the Ca2+ -PI signalling cascade may contribute to decreased expression or loss of specific thyroid functions in thyroid cancer cells.
Schöfl
C
C
Abteilung Klinische Endokrinologie, Medizinische Hochschule Hannover, Germany.
Rössig
L
L
Mader
T
T
Börger
J
J
Pötter
E
E
von zur Mühlen
A
A
Brabant
G
G
D000255:Adenosine Triphosphate / Q000502:physiology*; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002291:Carcinoma, Papillary / Q000378:metabolism; D018265:Carcinoma, Papillary, Follicular / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism / Q000502:physiology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects*; D019284:Thapsigargin / Q000494:pharmacology; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D002118:Calcium