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

Casagrande, Naike; Borghese, Cinzia; Agostini, Francesco; Durante, Cristina; Mazzucato, M.; Colombatti, Alfonso; Aldinucci, Donatella

doi:10.3390/ijms22063019

Cited by 32 publications

(18 citation statements)

References 64 publications

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“…A poly-HEMA coating in culture flasks has been used for the production of 3D heterotypic models of normal ovary and to study early ovarian cancer development ( Lawrenson et al, 2012 ). Ovarian cancer cell lines grown under poly-HEMA conditions in the presence of activated platelet releasate, formed spheroids faster and were more resistant to the chemotherapeutic agents cisplatin, carboplatin and paclitaxel ( Casagrande et al, 2021 ).…”

Section: 3d In Vitro Ovarian Cancer Modelsmentioning

confidence: 99%

Three-Dimensional Modelling of Ovarian Cancer: From Cell Lines to Organoids for Discovery and Personalized Medicine

Yee

Dickson

Muntasir

et al. 2022

Front. Bioeng. Biotechnol.

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Ovarian cancer has the highest mortality of all of the gynecological malignancies. There are several distinct histotypes of this malignancy characterized by specific molecular events and clinical behavior. These histotypes have differing responses to platinum-based drugs that have been the mainstay of therapy for ovarian cancer for decades. For histotypes that initially respond to a chemotherapeutic regime of carboplatin and paclitaxel such as high-grade serous ovarian cancer, the development of chemoresistance is common and underpins incurable disease. Recent discoveries have led to the clinical use of PARP (poly ADP ribose polymerase) inhibitors for ovarian cancers defective in homologous recombination repair, as well as the anti-angiogenic bevacizumab. While predictive molecular testing involving identification of a genomic scar and/or the presence of germline or somatic BRCA1 or BRCA2 mutation are in clinical use to inform the likely success of a PARP inhibitor, no similar tests are available to identify women likely to respond to bevacizumab. Functional tests to predict patient response to any drug are, in fact, essentially absent from clinical care. New drugs are needed to treat ovarian cancer. In this review, we discuss applications to address the currently unmet need of developing physiologically relevant in vitro and ex vivo models of ovarian cancer for fundamental discovery science, and personalized medicine approaches. Traditional two-dimensional (2D) in vitro cell culture of ovarian cancer lacks critical cell-to-cell interactions afforded by culture in three-dimensions. Additionally, modelling interactions with the tumor microenvironment, including the surface of organs in the peritoneal cavity that support metastatic growth of ovarian cancer, will improve the power of these models. Being able to reliably grow primary tumoroid cultures of ovarian cancer will improve the ability to recapitulate tumor heterogeneity. Three-dimensional (3D) modelling systems, from cell lines to organoid or tumoroid cultures, represent enhanced starting points from which improved translational outcomes for women with ovarian cancer will emerge.

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Section: 3d In Vitro Ovarian Cancer Modelsmentioning

confidence: 99%

Three-Dimensional Modelling of Ovarian Cancer: From Cell Lines to Organoids for Discovery and Personalized Medicine

Yee

Dickson

Muntasir

et al. 2022

Front. Bioeng. Biotechnol.

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“…We did not observe an association between the numbers of cells expressing only CD133 or only ALDH and clinical characteristics, but a high number of stem-like CD133+ALDHhigh cells before treatment were associated with a reduced progression-free survival in a multivariable analysis. It has previously been shown that platelets invert the cytostatic effects of carboplatin and paclitaxel on CD133+ and ALDH+ OC cells by secreting a number of cytokines and growth factors, in non-adherent conditions [ 46 ]. Further research is needed to understand the mechanisms of the interaction between OC circulating stem cells and other blood components.…”

Section: Discussionmentioning

confidence: 99%

The Detection of Stem-Like Circulating Tumor Cells Could Increase the Clinical Applicability of Liquid Biopsy in Ovarian Cancer

Генинг

Абакумова

Gafurbaeva

et al. 2021

Life

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Stem properties allow circulating tumor cells (CTCs) to survive in the bloodstream and initiate cancer progression. We aimed to assess the numbers of stem-like CTCs in patients with ovarian cancer (OC) before treatment and during first-line chemotherapy (CT). Flow cytometry was performed (Cytoflex S (Beckman Coulter, CA, USA)) using antibodies against CD45; epithelial markers EpCAM and cytokeratin (CK) 8,18; mesenchymal vimentin (vim); and stem-like CD44, CD133 and ALDH. This study included 38 stage I–IV OC patients (median age 66 (Q1–Q3 53–70)). The CK+vim- counts were higher (p = 0.012) and the CD133+ALDHhigh counts were lower (p = 0.010) before treatment in the neoadjuvant CT group than in the adjuvant group. The patients with ascites had more CK+vim- cells before treatment (p = 0.009) and less EpCAM-vim+ cells during treatment (p = 0.018) than the patients without ascites. All the CTC counts did not differ significantly in paired samples. Correlations were found between the CK-vim+ and CD133+ALDHhigh (r = 0.505, p = 0.027) and EpCAM-vim+ and ALDHhigh (r = 0.597, p = 0.004) cells before but not during treatment. Multivariate Cox regression analysis showed that progression-free survival was longer with the presence of surgical treatment (HR 0.06 95% CI 0.01–0.48, p = 0.009) and fewer CD133+ALDHveryhigh cells (HR 1.06 95% CI 1.02–1.12, p = 0.010). Thus, CD133+ALDH+ CTCs have the greatest prognostic potential in OC among the phenotypes studied.

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“…In addition, plateletderived chemokine RANTES and TSP1 (233) both increased the survival of paclitaxel-treated cancer cells (234). Casagrande et al suggested that platelet-secreted factors ((EGF, PDGF, TGFb, IGF and CCL5) protected cancer stem cells from paclitaxel, cisplatin and carboplatin (235). All above data prove the involvement of platelets in cancer chemoresistance.…”

Section: Platelet-related Chemoresistancementioning

confidence: 91%

“…Casagrande et al. suggested that platelet-secreted factors ((EGF, PDGF, TGF-β, IGF and CCL5) protected cancer stem cells from paclitaxel, cisplatin and carboplatin ( 235 ). All above data prove the involvement of platelets in cancer chemoresistance.…”

Section: Platelet–supported Cancer Progressionmentioning

confidence: 99%

Bidirectional Interaction Between Cancer Cells and Platelets Provides Potential Strategies for Cancer Therapies

Guo

Chang

et al. 2021

Front. Oncol.

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Platelets are essential components in the tumor microenvironment. For decades, clinical data have demonstrated that cancer patients have a high risk of thrombosis that is associated with adverse prognosis and decreased survival, indicating the involvement of platelets in cancer progression. Increasing evidence confirms that cancer cells are able to induce production and activation of platelets. Once activated, platelets serve as allies of cancer cells in tumor growth and metastasis. They can protect circulating tumor cells (CTCs) against the immune system and detachment-induced apoptosis while facilitating angiogenesis and tumor cell adhesion and invasion. Therefore, antiplatelet agents and platelet-based therapies should be developed for cancer treatment. Here, we discuss the mechanisms underlying the bidirectional cancer-platelet crosstalk and platelet-based therapeutic approaches.

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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

Cited by 32 publications

References 64 publications

Three-Dimensional Modelling of Ovarian Cancer: From Cell Lines to Organoids for Discovery and Personalized Medicine

Three-Dimensional Modelling of Ovarian Cancer: From Cell Lines to Organoids for Discovery and Personalized Medicine

The Detection of Stem-Like Circulating Tumor Cells Could Increase the Clinical Applicability of Liquid Biopsy in Ovarian Cancer

Bidirectional Interaction Between Cancer Cells and Platelets Provides Potential Strategies for Cancer Therapies

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