Nerve growth factor and retinoic acid interactions in the control of small cell lung cancer proliferation

Chiara Fiorentini, Marco Facchetti, Alessandra Finardi, Sandra Sigala, Marcelo Páez-Pereda, Emanuele Sher, PierFranco Spano, Cristina Missale

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Objective: Nerve growth factor (NGF) has antiproliferative and differentiating effects in neuroendocrine tumors. In cell lines derived from small cell lung cancer (SCLC), NGF treatment stimulates NGF receptor expression, activates NGF secretion, inhibits proliferation and abrogates invasion. Since these effects are lost upon NGF withdrawal, it is relevant to identify other differentiation factors that may co-operate with the NGF system to control SCLC growth and differentiation. Design: Retinoic acid (RA), which has been shown to inhibit cell transformation and proliferation, modulates the expression of NGF receptors and the sensitivity to NGF in different cell models. In the present study, we have investigated whether NGF and RA may interact to control the proliferation of SCLC cell lines. Methods: SCLC cells were exposed to 50 ng/ml NGF or 1 μM all-trans RA for different times. Cell proliferation was measured by the [3H]thymidine incorporation test and NGF receptor expression was evaluated by immunofluorescence. Results: We found that RA increased the expression of both trkA and p75 NGF receptors in NCI-N-592 and GLC8 cell lines and prevented the loss of both NGF production and NGF receptor expression occurring when NGF treatment was discontinued. As a result, RA, which did not inhibit the proliferation of untreated cells, abolished NGF withdrawal-related increase in cell proliferation both in vitro and in vivo, thus making permanent the antiproliferative effects of NGF. Conclusions: These data suggest that combined treatments with NGF and RA or mimicking drugs may represent a strategy to be further investigated for the treatment of SCLC.

Original languageEnglish
Pages (from-to)371-379
Number of pages9
JournalEuropean Journal of Endocrinology
Volume147
Issue number3
Publication statusPublished - Sep 2002

Fingerprint

Small Cell Lung Carcinoma
Nerve Growth Factor
Tretinoin
Nerve Growth Factor Receptor
Cell Proliferation
Cell Line
Nerve Growth Factor Receptors
Neuroendocrine Tumors
Therapeutics
Thymidine
Fluorescent Antibody Technique

ASJC Scopus subject areas

  • Endocrinology

Cite this

Fiorentini, C., Facchetti, M., Finardi, A., Sigala, S., Páez-Pereda, M., Sher, E., ... Missale, C. (2002). Nerve growth factor and retinoic acid interactions in the control of small cell lung cancer proliferation. European Journal of Endocrinology, 147(3), 371-379.

Nerve growth factor and retinoic acid interactions in the control of small cell lung cancer proliferation. / Fiorentini, Chiara; Facchetti, Marco; Finardi, Alessandra; Sigala, Sandra; Páez-Pereda, Marcelo; Sher, Emanuele; Spano, PierFranco; Missale, Cristina.

In: European Journal of Endocrinology, Vol. 147, No. 3, 09.2002, p. 371-379.

Research output: Contribution to journalArticle

Fiorentini, C, Facchetti, M, Finardi, A, Sigala, S, Páez-Pereda, M, Sher, E, Spano, P & Missale, C 2002, 'Nerve growth factor and retinoic acid interactions in the control of small cell lung cancer proliferation', European Journal of Endocrinology, vol. 147, no. 3, pp. 371-379.
Fiorentini C, Facchetti M, Finardi A, Sigala S, Páez-Pereda M, Sher E et al. Nerve growth factor and retinoic acid interactions in the control of small cell lung cancer proliferation. European Journal of Endocrinology. 2002 Sep;147(3):371-379.
Fiorentini, Chiara ; Facchetti, Marco ; Finardi, Alessandra ; Sigala, Sandra ; Páez-Pereda, Marcelo ; Sher, Emanuele ; Spano, PierFranco ; Missale, Cristina. / Nerve growth factor and retinoic acid interactions in the control of small cell lung cancer proliferation. In: European Journal of Endocrinology. 2002 ; Vol. 147, No. 3. pp. 371-379.
@article{d4234f2c1bf34428b168cdc3a1f90b5e,
title = "Nerve growth factor and retinoic acid interactions in the control of small cell lung cancer proliferation",
abstract = "Objective: Nerve growth factor (NGF) has antiproliferative and differentiating effects in neuroendocrine tumors. In cell lines derived from small cell lung cancer (SCLC), NGF treatment stimulates NGF receptor expression, activates NGF secretion, inhibits proliferation and abrogates invasion. Since these effects are lost upon NGF withdrawal, it is relevant to identify other differentiation factors that may co-operate with the NGF system to control SCLC growth and differentiation. Design: Retinoic acid (RA), which has been shown to inhibit cell transformation and proliferation, modulates the expression of NGF receptors and the sensitivity to NGF in different cell models. In the present study, we have investigated whether NGF and RA may interact to control the proliferation of SCLC cell lines. Methods: SCLC cells were exposed to 50 ng/ml NGF or 1 μM all-trans RA for different times. Cell proliferation was measured by the [3H]thymidine incorporation test and NGF receptor expression was evaluated by immunofluorescence. Results: We found that RA increased the expression of both trkA and p75 NGF receptors in NCI-N-592 and GLC8 cell lines and prevented the loss of both NGF production and NGF receptor expression occurring when NGF treatment was discontinued. As a result, RA, which did not inhibit the proliferation of untreated cells, abolished NGF withdrawal-related increase in cell proliferation both in vitro and in vivo, thus making permanent the antiproliferative effects of NGF. Conclusions: These data suggest that combined treatments with NGF and RA or mimicking drugs may represent a strategy to be further investigated for the treatment of SCLC.",
author = "Chiara Fiorentini and Marco Facchetti and Alessandra Finardi and Sandra Sigala and Marcelo P{\'a}ez-Pereda and Emanuele Sher and PierFranco Spano and Cristina Missale",
year = "2002",
month = "9",
language = "English",
volume = "147",
pages = "371--379",
journal = "European Journal of Endocrinology",
issn = "0804-4643",
publisher = "BioScientifica Ltd.",
number = "3",

}

TY - JOUR

T1 - Nerve growth factor and retinoic acid interactions in the control of small cell lung cancer proliferation

AU - Fiorentini, Chiara

AU - Facchetti, Marco

AU - Finardi, Alessandra

AU - Sigala, Sandra

AU - Páez-Pereda, Marcelo

AU - Sher, Emanuele

AU - Spano, PierFranco

AU - Missale, Cristina

PY - 2002/9

Y1 - 2002/9

N2 - Objective: Nerve growth factor (NGF) has antiproliferative and differentiating effects in neuroendocrine tumors. In cell lines derived from small cell lung cancer (SCLC), NGF treatment stimulates NGF receptor expression, activates NGF secretion, inhibits proliferation and abrogates invasion. Since these effects are lost upon NGF withdrawal, it is relevant to identify other differentiation factors that may co-operate with the NGF system to control SCLC growth and differentiation. Design: Retinoic acid (RA), which has been shown to inhibit cell transformation and proliferation, modulates the expression of NGF receptors and the sensitivity to NGF in different cell models. In the present study, we have investigated whether NGF and RA may interact to control the proliferation of SCLC cell lines. Methods: SCLC cells were exposed to 50 ng/ml NGF or 1 μM all-trans RA for different times. Cell proliferation was measured by the [3H]thymidine incorporation test and NGF receptor expression was evaluated by immunofluorescence. Results: We found that RA increased the expression of both trkA and p75 NGF receptors in NCI-N-592 and GLC8 cell lines and prevented the loss of both NGF production and NGF receptor expression occurring when NGF treatment was discontinued. As a result, RA, which did not inhibit the proliferation of untreated cells, abolished NGF withdrawal-related increase in cell proliferation both in vitro and in vivo, thus making permanent the antiproliferative effects of NGF. Conclusions: These data suggest that combined treatments with NGF and RA or mimicking drugs may represent a strategy to be further investigated for the treatment of SCLC.

AB - Objective: Nerve growth factor (NGF) has antiproliferative and differentiating effects in neuroendocrine tumors. In cell lines derived from small cell lung cancer (SCLC), NGF treatment stimulates NGF receptor expression, activates NGF secretion, inhibits proliferation and abrogates invasion. Since these effects are lost upon NGF withdrawal, it is relevant to identify other differentiation factors that may co-operate with the NGF system to control SCLC growth and differentiation. Design: Retinoic acid (RA), which has been shown to inhibit cell transformation and proliferation, modulates the expression of NGF receptors and the sensitivity to NGF in different cell models. In the present study, we have investigated whether NGF and RA may interact to control the proliferation of SCLC cell lines. Methods: SCLC cells were exposed to 50 ng/ml NGF or 1 μM all-trans RA for different times. Cell proliferation was measured by the [3H]thymidine incorporation test and NGF receptor expression was evaluated by immunofluorescence. Results: We found that RA increased the expression of both trkA and p75 NGF receptors in NCI-N-592 and GLC8 cell lines and prevented the loss of both NGF production and NGF receptor expression occurring when NGF treatment was discontinued. As a result, RA, which did not inhibit the proliferation of untreated cells, abolished NGF withdrawal-related increase in cell proliferation both in vitro and in vivo, thus making permanent the antiproliferative effects of NGF. Conclusions: These data suggest that combined treatments with NGF and RA or mimicking drugs may represent a strategy to be further investigated for the treatment of SCLC.

UR - http://www.scopus.com/inward/record.url?scp=0036737930&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036737930&partnerID=8YFLogxK

M3 - Article

C2 - 12213675

AN - SCOPUS:0036737930

VL - 147

SP - 371

EP - 379

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

SN - 0804-4643

IS - 3

ER -