Characterization of the functional and growth properties of long-term cell cultures established from a human somatostatinoma.
In somatostatinoma, a rare malignant somatostatin (SST)-secreting neoplasia, tumour regression is rarely observed, implying the need for novel antiproliferative strategies. Here, we characterized a long-term culture (SST-secreting cancer (SS-C cells)) established from a human somatostatinoma. High concentrations of SST and chromogranin A were released by SS-C cells and SST release was stimulated by depolarizing stimuli and inhibited by the SST analogue, octreotide. SS-C cells expressed mRNA for SST receptor (SSTR) subtypes 1, 2 and 4, being also able to bind native SST. Moreover, SS-C cells were positively stained with an antibody to SSTR2. SS-C cells also expressed interferon-gamma (IFN-gamma) receptor mRNA and measurable telomerase activity. Our findings indicate that in vitro exposure of SS-C cells to native SST-28, to octreotide, to IFN-gamma, or to 3'-azido-3'deoxythymidine (AZT), a telomerase inhibitor, results in inhibition of SS-C cell proliferation. Concomitant with growth inhibition, apoptosis was detected in SST-, octreotide-, IFN-gamma- or AZT-treated SS-C cell cultures. Taken together our results characterized native SST, SST analogues, IFN-gamma and a telomerase inhibitor as growth-inhibiting and proapoptotic stimuli in cultured human somatostatinoma cells. Based on these findings, the potential of SST analogues, IFN-gamma and AZT, alone or in combination, should be further explored in the medical treatment of somatostatinoma.
Galli
G
G
Department of Internal Medicine, University of Florence Medical School, Viale Pieraccini 6, 50139 Florence, Italy.
Zonefrati
R
R
Gozzini
A
A
Mavilia
C
C
Martineti
V
V
Tognarini
I
I
Nesi
G
G
Marcucci
T
T
Tonelli
F
F
Tommasi
M
M
Raggi
C Casini
CC
Pinzani
P
P
Brandi
M L
ML
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D053379:Chromogranin A; D002864:Chromogranins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000494:pharmacology; D007580:Jejunal Neoplasms / Q000378:metabolism / Q000473:pathology*; D015282:Octreotide / Q000494:pharmacology; D012333:RNA, Messenger; D017481:Receptors, Somatostatin / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism*; D013005:Somatostatinoma / Q000378:metabolism / Q000473:pathology*; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015215:Zidovudine / Q000494:pharmacology
D019380:Anti-HIV Agents; D018931:Antineoplastic Agents, Hormonal; D053379:Chromogranin A; D002864:Chromogranins; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; D015215:Zidovudine; D013004:Somatostatin; D007371:Interferon-gamma; C093733:somatostatin receptor 2; D019098:Telomerase; D015282:Octreotide