Corsi, Francesca and Capradossi, Francesco and Pelliccia, Andrea and Briganti, Stefania and Bruni, Emanuele and Traversa, Enrico and Torino, Francesco and Reichle, Albrecht and Ghibelli, Lina (2022) Apoptosis as Driver of Therapy-Induced Cancer Repopulation and Acquired Cell-Resistance (CRAC): A Simple In Vitro Model of Phoenix Rising in Prostate Cancer. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 23 (3): 1152. ISSN , 1422-0067
Full text not available from this repository. (Request a copy)Abstract
Apoptotic cells stimulate compensatory proliferation through the caspase-3-cPLA-2-COX-2-PGE-2-STAT3 Phoenix Rising pathway as a healing process in normal tissues. Phoenix Rising is however usurped in cancer, potentially nullifying pro-apoptotic therapies. Cytotoxic therapies also promote cancer cell plasticity through epigenetic reprogramming, leading to epithelial-to-mesenchymal-transition (EMT), chemo-resistance and tumor progression. We explored the relationship between such scenarios, setting-up an innovative, straightforward one-pot in vitro model of therapy-induced prostate cancer repopulation. Cancer (castration-resistant PC3 and androgen-sensitive LNCaP), or normal (RWPE-1) prostate cells, are treated with etoposide and left recovering for 18 days. After a robust apoptotic phase, PC3 setup a coordinate tissue-like response, repopulating and acquiring EMT and chemo-resistance; repopulation occurs via Phoenix Rising, being dependent on high PGE-2 levels achieved through caspase-3-promoted signaling; epigenetic inhibitors interrupt Phoenix Rising after PGE-2, preventing repopulation. Instead, RWPE-1 repopulate via Phoenix Rising without reprogramming, EMT or chemo-resistance, indicating that only cancer cells require reprogramming to complete Phoenix Rising. Intriguingly, LNCaP stop Phoenix-Rising after PGE-2, failing repopulating, suggesting that the propensity to engage/complete Phoenix Rising may influence the outcome of pro-apoptotic therapies. Concluding, we established a reliable system where to study prostate cancer repopulation, showing that epigenetic reprogramming assists Phoenix Rising to promote post-therapy cancer repopulation and acquired cell-resistance (CRAC).
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TUMOR-CELLS; STEM-CELLS; PROLIFERATION; EMT; CHEMOTHERAPY; COMBINATION; SENESCENCE; INHIBITORS; INDUCTION; SURVIVAL; caspase-3; chemoresistance; XIAP; PC3; LNCaP; PGE-2; EMT |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Feb 2024 14:55 |
| Last Modified: | 29 Feb 2024 14:55 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58340 |
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