In Ovarian Cancer Multicellular Spheroids, Platelet Releasate Promotes Growth, Expansion of ALDH+ and CD133+Cancer Stem Cells, and Protection against the Cytotoxic Effects of Cisplatin, Carboplatin and Paclitaxel

被引：36
作者：
Casagrande, Naike [1 ]
Borghese, Cinzia [1 ]
Agostini, Francesco [2 ]
Durante, Cristina [2 ]
Mazzucato, Mario [2 ]
Colombatti, Alfonso [1 ]
Aldinucci, Donatella [1 ]
机构：
[1] IRCCS, Ctr Riferimento Oncol Aviano CRO, Mol Oncol Unit, I-33081 Aviano, Italy
[2] IRCCS, Ctr Riferimento Oncol Aviano CRO, Stem Cell Unit, I-33081 Aviano, Italy
来源：
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2021年 / 22卷 / 06期
关键词：
platelet releasate; ovarian cancer stem cells; ovarian cancer spheroids; anticancer therapy; drug resistance; cisplatin; carboplatin; paclitaxel;
D O I：
10.3390/ijms22063019
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
A high platelet count is associated with a poor prognosis in ovarian cancer (OvCa). Despite good clinical responses with platinating agents in combination with taxanes, numerous OvCa patients relapse due to chemotherapy resistance. Here, we report that treatment of OvCa cells A2780, OVCAR5 and MDAH with releasate from activated platelets (PR) promoted multicellular tumor spheroid (MCTS) formation. These OvCa-MCTSs had increased percentages of CD133+ and aldehyde dehydrogenase (ALDH)+ cells, bona fide markers of OvCa cancer stem cells (CSCs). PR increased OVCAR5- and MDAH-MCTS viability and decreased the cytotoxic and pro-apoptotic effects of paclitaxel, cisplatin and carboplatin. PR increased the volume of spontaneously formed OVCAR8-MCTSs and counteracted their size reduction due to cisplatin, carboplatin and paclitaxel treatment. PR promoted the survival of ALDH+ and CD133+ OvCa cells during cisplatin, carboplatin and paclitaxel treatment. In conclusion, molecules and growth factors released by activated platelets (EGF, PDGF, TGF-beta, IGF and CCL5) may protect tumor cells from chemotherapy by promoting the expansion of ALDH+ and CD133+ OvCa-CSCs, favoring drug resistance and tumor relapse.
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页码：1 / 11
页数：11
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