The Extracellular Matrix Influences Ovarian Carcinoma Cells’ Sensitivity to Cisplatinum: A First Step towards Personalized Medicine
The development of personalized therapies for ovarian carcinoma patients is still hampered by several limitations, mainly the difficulty of predicting patients’ responses to chemotherapy in tumor cells isolated from peritoneal fluids. The main reason for the low predictive power of in vitro assays i...
Main Authors: | , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2020-05-01
|
Series: | Cancers |
Subjects: | |
Online Access: | https://www.mdpi.com/2072-6694/12/5/1175 |
_version_ | 1797568672317833216 |
---|---|
author | Andrea Balduit Chiara Agostinis Alessandro Mangogna Veronica Maggi Gabriella Zito Federico Romano Andrea Romano Rita Ceccherini Gabriele Grassi Serena Bonin Deborah Bonazza Fabrizio Zanconati Giuseppe Ricci Roberta Bulla |
author_facet | Andrea Balduit Chiara Agostinis Alessandro Mangogna Veronica Maggi Gabriella Zito Federico Romano Andrea Romano Rita Ceccherini Gabriele Grassi Serena Bonin Deborah Bonazza Fabrizio Zanconati Giuseppe Ricci Roberta Bulla |
author_sort | Andrea Balduit |
collection | DOAJ |
description | The development of personalized therapies for ovarian carcinoma patients is still hampered by several limitations, mainly the difficulty of predicting patients’ responses to chemotherapy in tumor cells isolated from peritoneal fluids. The main reason for the low predictive power of in vitro assays is related to the modification of the cancer cells’ phenotype induced by the culture conditions, which results in changes to the activation state and drug sensitivity of tumor cells compared to their in vivo properties. We have defined the optimal culture conditions to set up a prognostic test to predict high-grade serous ovarian carcinoma (HGSOC) patients’ responses to platinum chemotherapy. We evaluated the effects of hyaluronic acid (HA) and fibronectin matrices and the contribution of freezing/thawing processes to the cell response to platinum-based treatment, collecting spheroids from the ascitic fluids of 13 patients with stage II or III HGSOC. Our findings indicated that an efficient model used to generate predictive data for in vivo sensitivity to platinum is culturing fresh spheroids on HA, avoiding the use of previously frozen primary tumor cells. The establishment of this easy, reproducible and standardized testing method can significantly contribute to an improvement in therapeutic effectiveness, thus bringing the prospect of personalized therapy closer for ovarian carcinoma patients. |
first_indexed | 2024-03-10T20:00:14Z |
format | Article |
id | doaj.art-5498fb33971943c88228be018c20a2f1 |
institution | Directory Open Access Journal |
issn | 2072-6694 |
language | English |
last_indexed | 2024-03-10T20:00:14Z |
publishDate | 2020-05-01 |
publisher | MDPI AG |
record_format | Article |
series | Cancers |
spelling | doaj.art-5498fb33971943c88228be018c20a2f12023-11-19T23:39:35ZengMDPI AGCancers2072-66942020-05-01125117510.3390/cancers12051175The Extracellular Matrix Influences Ovarian Carcinoma Cells’ Sensitivity to Cisplatinum: A First Step towards Personalized MedicineAndrea Balduit0Chiara Agostinis1Alessandro Mangogna2Veronica Maggi3Gabriella Zito4Federico Romano5Andrea Romano6Rita Ceccherini7Gabriele Grassi8Serena Bonin9Deborah Bonazza10Fabrizio Zanconati11Giuseppe Ricci12Roberta Bulla13Department of Life Sciences, University of Trieste, 34127 Trieste, ItalyInstitute for Maternal and Child Health, IRCCS Burlo Garofolo, 34134 Trieste, ItalyDepartment of Life Sciences, University of Trieste, 34127 Trieste, ItalyDepartment of Medical, Surgical and Health Science, University of Trieste, 34129 Trieste, ItalyInstitute for Maternal and Child Health, IRCCS Burlo Garofolo, 34134 Trieste, ItalyInstitute for Maternal and Child Health, IRCCS Burlo Garofolo, 34134 Trieste, ItalyDepartment of Medical, Surgical and Health Science, University of Trieste, 34129 Trieste, ItalyCentro Sociale Oncologico, OSARF, Azienda Sanitaria Universitaria Giuliano Isontina, 34127 Trieste, ItalyDepartment of Life Sciences, University of Trieste, 34127 Trieste, ItalyDepartment of Medical, Surgical and Health Science, University of Trieste, 34129 Trieste, ItalyDepartment of Medical, Surgical and Health Science, University of Trieste, 34129 Trieste, ItalyDepartment of Medical, Surgical and Health Science, University of Trieste, 34129 Trieste, ItalyInstitute for Maternal and Child Health, IRCCS Burlo Garofolo, 34134 Trieste, ItalyDepartment of Life Sciences, University of Trieste, 34127 Trieste, ItalyThe development of personalized therapies for ovarian carcinoma patients is still hampered by several limitations, mainly the difficulty of predicting patients’ responses to chemotherapy in tumor cells isolated from peritoneal fluids. The main reason for the low predictive power of in vitro assays is related to the modification of the cancer cells’ phenotype induced by the culture conditions, which results in changes to the activation state and drug sensitivity of tumor cells compared to their in vivo properties. We have defined the optimal culture conditions to set up a prognostic test to predict high-grade serous ovarian carcinoma (HGSOC) patients’ responses to platinum chemotherapy. We evaluated the effects of hyaluronic acid (HA) and fibronectin matrices and the contribution of freezing/thawing processes to the cell response to platinum-based treatment, collecting spheroids from the ascitic fluids of 13 patients with stage II or III HGSOC. Our findings indicated that an efficient model used to generate predictive data for in vivo sensitivity to platinum is culturing fresh spheroids on HA, avoiding the use of previously frozen primary tumor cells. The establishment of this easy, reproducible and standardized testing method can significantly contribute to an improvement in therapeutic effectiveness, thus bringing the prospect of personalized therapy closer for ovarian carcinoma patients.https://www.mdpi.com/2072-6694/12/5/1175ovarian cancerspheroidschemoresistancehyaluronic acidfibronectinpersonalized medicine |
spellingShingle | Andrea Balduit Chiara Agostinis Alessandro Mangogna Veronica Maggi Gabriella Zito Federico Romano Andrea Romano Rita Ceccherini Gabriele Grassi Serena Bonin Deborah Bonazza Fabrizio Zanconati Giuseppe Ricci Roberta Bulla The Extracellular Matrix Influences Ovarian Carcinoma Cells’ Sensitivity to Cisplatinum: A First Step towards Personalized Medicine Cancers ovarian cancer spheroids chemoresistance hyaluronic acid fibronectin personalized medicine |
title | The Extracellular Matrix Influences Ovarian Carcinoma Cells’ Sensitivity to Cisplatinum: A First Step towards Personalized Medicine |
title_full | The Extracellular Matrix Influences Ovarian Carcinoma Cells’ Sensitivity to Cisplatinum: A First Step towards Personalized Medicine |
title_fullStr | The Extracellular Matrix Influences Ovarian Carcinoma Cells’ Sensitivity to Cisplatinum: A First Step towards Personalized Medicine |
title_full_unstemmed | The Extracellular Matrix Influences Ovarian Carcinoma Cells’ Sensitivity to Cisplatinum: A First Step towards Personalized Medicine |
title_short | The Extracellular Matrix Influences Ovarian Carcinoma Cells’ Sensitivity to Cisplatinum: A First Step towards Personalized Medicine |
title_sort | extracellular matrix influences ovarian carcinoma cells sensitivity to cisplatinum a first step towards personalized medicine |
topic | ovarian cancer spheroids chemoresistance hyaluronic acid fibronectin personalized medicine |
url | https://www.mdpi.com/2072-6694/12/5/1175 |
work_keys_str_mv | AT andreabalduit theextracellularmatrixinfluencesovariancarcinomacellssensitivitytocisplatinumafirststeptowardspersonalizedmedicine AT chiaraagostinis theextracellularmatrixinfluencesovariancarcinomacellssensitivitytocisplatinumafirststeptowardspersonalizedmedicine AT alessandromangogna theextracellularmatrixinfluencesovariancarcinomacellssensitivitytocisplatinumafirststeptowardspersonalizedmedicine AT veronicamaggi theextracellularmatrixinfluencesovariancarcinomacellssensitivitytocisplatinumafirststeptowardspersonalizedmedicine AT gabriellazito theextracellularmatrixinfluencesovariancarcinomacellssensitivitytocisplatinumafirststeptowardspersonalizedmedicine AT federicoromano theextracellularmatrixinfluencesovariancarcinomacellssensitivitytocisplatinumafirststeptowardspersonalizedmedicine AT andrearomano theextracellularmatrixinfluencesovariancarcinomacellssensitivitytocisplatinumafirststeptowardspersonalizedmedicine AT ritaceccherini theextracellularmatrixinfluencesovariancarcinomacellssensitivitytocisplatinumafirststeptowardspersonalizedmedicine AT gabrielegrassi theextracellularmatrixinfluencesovariancarcinomacellssensitivitytocisplatinumafirststeptowardspersonalizedmedicine AT serenabonin theextracellularmatrixinfluencesovariancarcinomacellssensitivitytocisplatinumafirststeptowardspersonalizedmedicine AT deborahbonazza theextracellularmatrixinfluencesovariancarcinomacellssensitivitytocisplatinumafirststeptowardspersonalizedmedicine AT fabriziozanconati theextracellularmatrixinfluencesovariancarcinomacellssensitivitytocisplatinumafirststeptowardspersonalizedmedicine AT giuseppericci theextracellularmatrixinfluencesovariancarcinomacellssensitivitytocisplatinumafirststeptowardspersonalizedmedicine AT robertabulla theextracellularmatrixinfluencesovariancarcinomacellssensitivitytocisplatinumafirststeptowardspersonalizedmedicine AT andreabalduit extracellularmatrixinfluencesovariancarcinomacellssensitivitytocisplatinumafirststeptowardspersonalizedmedicine AT chiaraagostinis extracellularmatrixinfluencesovariancarcinomacellssensitivitytocisplatinumafirststeptowardspersonalizedmedicine AT alessandromangogna extracellularmatrixinfluencesovariancarcinomacellssensitivitytocisplatinumafirststeptowardspersonalizedmedicine AT veronicamaggi extracellularmatrixinfluencesovariancarcinomacellssensitivitytocisplatinumafirststeptowardspersonalizedmedicine AT gabriellazito extracellularmatrixinfluencesovariancarcinomacellssensitivitytocisplatinumafirststeptowardspersonalizedmedicine AT federicoromano extracellularmatrixinfluencesovariancarcinomacellssensitivitytocisplatinumafirststeptowardspersonalizedmedicine AT andrearomano extracellularmatrixinfluencesovariancarcinomacellssensitivitytocisplatinumafirststeptowardspersonalizedmedicine AT ritaceccherini extracellularmatrixinfluencesovariancarcinomacellssensitivitytocisplatinumafirststeptowardspersonalizedmedicine AT gabrielegrassi extracellularmatrixinfluencesovariancarcinomacellssensitivitytocisplatinumafirststeptowardspersonalizedmedicine AT serenabonin extracellularmatrixinfluencesovariancarcinomacellssensitivitytocisplatinumafirststeptowardspersonalizedmedicine AT deborahbonazza extracellularmatrixinfluencesovariancarcinomacellssensitivitytocisplatinumafirststeptowardspersonalizedmedicine AT fabriziozanconati extracellularmatrixinfluencesovariancarcinomacellssensitivitytocisplatinumafirststeptowardspersonalizedmedicine AT giuseppericci extracellularmatrixinfluencesovariancarcinomacellssensitivitytocisplatinumafirststeptowardspersonalizedmedicine AT robertabulla extracellularmatrixinfluencesovariancarcinomacellssensitivitytocisplatinumafirststeptowardspersonalizedmedicine |