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Neuroendocrine Transdifferentiation in Human Prostate Cancer Cells: An Integrated Approach
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| Zeitschriftentitel: | Cancer Research |
|---|---|
| Personen und Körperschaften: | , , , , , , , |
| In: | Cancer Research, 75, 2015, 15, S. 2975-2986 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
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| Schlagwörter: |
| author_facet |
Cerasuolo, Marianna Paris, Debora Iannotti, Fabio A. Melck, Dominique Verde, Roberta Mazzarella, Enrico Motta, Andrea Ligresti, Alessia Cerasuolo, Marianna Paris, Debora Iannotti, Fabio A. Melck, Dominique Verde, Roberta Mazzarella, Enrico Motta, Andrea Ligresti, Alessia |
|---|---|
| author |
Cerasuolo, Marianna Paris, Debora Iannotti, Fabio A. Melck, Dominique Verde, Roberta Mazzarella, Enrico Motta, Andrea Ligresti, Alessia |
| spellingShingle |
Cerasuolo, Marianna Paris, Debora Iannotti, Fabio A. Melck, Dominique Verde, Roberta Mazzarella, Enrico Motta, Andrea Ligresti, Alessia Cancer Research Neuroendocrine Transdifferentiation in Human Prostate Cancer Cells: An Integrated Approach Cancer Research Oncology |
| author_sort |
cerasuolo, marianna |
| spelling |
Cerasuolo, Marianna Paris, Debora Iannotti, Fabio A. Melck, Dominique Verde, Roberta Mazzarella, Enrico Motta, Andrea Ligresti, Alessia 0008-5472 1538-7445 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/0008-5472.can-14-3830 <jats:title>Abstract</jats:title> <jats:p>Prostate cancer is highly sensitive to hormone therapy because androgens are essential for prostate cancer cell growth. However, with the nearly invariable progression of this disease to androgen independence, endocrine therapy ultimately fails to control prostate cancer in most patients. Androgen-independent acquisition may involve neuroendocrine transdifferentiation, but there is little knowledge about this process, which is presently controversial. In this study, we investigated this question in a novel model of human androgen-dependent LNCaP cells cultured for long periods in hormone-deprived conditions. Strikingly, characterization of the neuroendocrine phenotype by transcriptomic, metabolomic, and other statistically integrated analyses showed how hormone-deprived LNCaP cells could transdifferentiate to a nonmalignantneuroendocrine phenotype. Notably, conditioned media from neuroendocrine-like cells affected LNCaP cell proliferation. Predictive in silico models illustrated how after an initial period, when LNCaP cell survival was compromised by an arising population of neuroendocrine-like cells, a sudden trend reversal occurred in which the neuroendocrine-like cells functioned to sustain the remaining androgen-dependent LNCaP cells. Our findings provide direct biologic and molecular support for the concept that neuroendocrine transdifferentiation in prostate cancer cell populations influences the progression to androgen independence. Cancer Res; 75(15); 2975–86. ©2015 AACR.</jats:p> Neuroendocrine Transdifferentiation in Human Prostate Cancer Cells: An Integrated Approach Cancer Research |
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| title |
Neuroendocrine Transdifferentiation in Human Prostate Cancer Cells: An Integrated Approach |
| title_unstemmed |
Neuroendocrine Transdifferentiation in Human Prostate Cancer Cells: An Integrated Approach |
| title_full |
Neuroendocrine Transdifferentiation in Human Prostate Cancer Cells: An Integrated Approach |
| title_fullStr |
Neuroendocrine Transdifferentiation in Human Prostate Cancer Cells: An Integrated Approach |
| title_full_unstemmed |
Neuroendocrine Transdifferentiation in Human Prostate Cancer Cells: An Integrated Approach |
| title_short |
Neuroendocrine Transdifferentiation in Human Prostate Cancer Cells: An Integrated Approach |
| title_sort |
neuroendocrine transdifferentiation in human prostate cancer cells: an integrated approach |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1158/0008-5472.can-14-3830 |
| publishDate |
2015 |
| physical |
2975-2986 |
| description |
<jats:title>Abstract</jats:title>
<jats:p>Prostate cancer is highly sensitive to hormone therapy because androgens are essential for prostate cancer cell growth. However, with the nearly invariable progression of this disease to androgen independence, endocrine therapy ultimately fails to control prostate cancer in most patients. Androgen-independent acquisition may involve neuroendocrine transdifferentiation, but there is little knowledge about this process, which is presently controversial. In this study, we investigated this question in a novel model of human androgen-dependent LNCaP cells cultured for long periods in hormone-deprived conditions. Strikingly, characterization of the neuroendocrine phenotype by transcriptomic, metabolomic, and other statistically integrated analyses showed how hormone-deprived LNCaP cells could transdifferentiate to a nonmalignantneuroendocrine phenotype. Notably, conditioned media from neuroendocrine-like cells affected LNCaP cell proliferation. Predictive in silico models illustrated how after an initial period, when LNCaP cell survival was compromised by an arising population of neuroendocrine-like cells, a sudden trend reversal occurred in which the neuroendocrine-like cells functioned to sustain the remaining androgen-dependent LNCaP cells. Our findings provide direct biologic and molecular support for the concept that neuroendocrine transdifferentiation in prostate cancer cell populations influences the progression to androgen independence. Cancer Res; 75(15); 2975–86. ©2015 AACR.</jats:p> |
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| author | Cerasuolo, Marianna, Paris, Debora, Iannotti, Fabio A., Melck, Dominique, Verde, Roberta, Mazzarella, Enrico, Motta, Andrea, Ligresti, Alessia |
| author_facet | Cerasuolo, Marianna, Paris, Debora, Iannotti, Fabio A., Melck, Dominique, Verde, Roberta, Mazzarella, Enrico, Motta, Andrea, Ligresti, Alessia, Cerasuolo, Marianna, Paris, Debora, Iannotti, Fabio A., Melck, Dominique, Verde, Roberta, Mazzarella, Enrico, Motta, Andrea, Ligresti, Alessia |
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| description | <jats:title>Abstract</jats:title> <jats:p>Prostate cancer is highly sensitive to hormone therapy because androgens are essential for prostate cancer cell growth. However, with the nearly invariable progression of this disease to androgen independence, endocrine therapy ultimately fails to control prostate cancer in most patients. Androgen-independent acquisition may involve neuroendocrine transdifferentiation, but there is little knowledge about this process, which is presently controversial. In this study, we investigated this question in a novel model of human androgen-dependent LNCaP cells cultured for long periods in hormone-deprived conditions. Strikingly, characterization of the neuroendocrine phenotype by transcriptomic, metabolomic, and other statistically integrated analyses showed how hormone-deprived LNCaP cells could transdifferentiate to a nonmalignantneuroendocrine phenotype. Notably, conditioned media from neuroendocrine-like cells affected LNCaP cell proliferation. Predictive in silico models illustrated how after an initial period, when LNCaP cell survival was compromised by an arising population of neuroendocrine-like cells, a sudden trend reversal occurred in which the neuroendocrine-like cells functioned to sustain the remaining androgen-dependent LNCaP cells. Our findings provide direct biologic and molecular support for the concept that neuroendocrine transdifferentiation in prostate cancer cell populations influences the progression to androgen independence. Cancer Res; 75(15); 2975–86. ©2015 AACR.</jats:p> |
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| imprint_str_mv | American Association for Cancer Research (AACR), 2015 |
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| spelling | Cerasuolo, Marianna Paris, Debora Iannotti, Fabio A. Melck, Dominique Verde, Roberta Mazzarella, Enrico Motta, Andrea Ligresti, Alessia 0008-5472 1538-7445 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/0008-5472.can-14-3830 <jats:title>Abstract</jats:title> <jats:p>Prostate cancer is highly sensitive to hormone therapy because androgens are essential for prostate cancer cell growth. However, with the nearly invariable progression of this disease to androgen independence, endocrine therapy ultimately fails to control prostate cancer in most patients. Androgen-independent acquisition may involve neuroendocrine transdifferentiation, but there is little knowledge about this process, which is presently controversial. In this study, we investigated this question in a novel model of human androgen-dependent LNCaP cells cultured for long periods in hormone-deprived conditions. Strikingly, characterization of the neuroendocrine phenotype by transcriptomic, metabolomic, and other statistically integrated analyses showed how hormone-deprived LNCaP cells could transdifferentiate to a nonmalignantneuroendocrine phenotype. Notably, conditioned media from neuroendocrine-like cells affected LNCaP cell proliferation. Predictive in silico models illustrated how after an initial period, when LNCaP cell survival was compromised by an arising population of neuroendocrine-like cells, a sudden trend reversal occurred in which the neuroendocrine-like cells functioned to sustain the remaining androgen-dependent LNCaP cells. Our findings provide direct biologic and molecular support for the concept that neuroendocrine transdifferentiation in prostate cancer cell populations influences the progression to androgen independence. Cancer Res; 75(15); 2975–86. ©2015 AACR.</jats:p> Neuroendocrine Transdifferentiation in Human Prostate Cancer Cells: An Integrated Approach Cancer Research |
| spellingShingle | Cerasuolo, Marianna, Paris, Debora, Iannotti, Fabio A., Melck, Dominique, Verde, Roberta, Mazzarella, Enrico, Motta, Andrea, Ligresti, Alessia, Cancer Research, Neuroendocrine Transdifferentiation in Human Prostate Cancer Cells: An Integrated Approach, Cancer Research, Oncology |
| title | Neuroendocrine Transdifferentiation in Human Prostate Cancer Cells: An Integrated Approach |
| title_full | Neuroendocrine Transdifferentiation in Human Prostate Cancer Cells: An Integrated Approach |
| title_fullStr | Neuroendocrine Transdifferentiation in Human Prostate Cancer Cells: An Integrated Approach |
| title_full_unstemmed | Neuroendocrine Transdifferentiation in Human Prostate Cancer Cells: An Integrated Approach |
| title_short | Neuroendocrine Transdifferentiation in Human Prostate Cancer Cells: An Integrated Approach |
| title_sort | neuroendocrine transdifferentiation in human prostate cancer cells: an integrated approach |
| title_unstemmed | Neuroendocrine Transdifferentiation in Human Prostate Cancer Cells: An Integrated Approach |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1158/0008-5472.can-14-3830 |