Curcumin Treatment Identifies Therapeutic Targets within Biomarkers of Liver Colonization by Highly Invasive Mesothelioma Cells—Potential Links with Sarcomas
Investigations of liver metastatic colonization suggest that the microenvironment is preordained to be intrinsically hospitable to the invasive cancer cells. To identify molecular determinants of that organotropism and potential therapeutic targets, we conducted proteomic analyses of the liver in an...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2020-11-01
|
Series: | Cancers |
Subjects: | |
Online Access: | https://www.mdpi.com/2072-6694/12/11/3384 |
_version_ | 1797547865274318848 |
---|---|
author | Daniel L. Pouliquen Alice Boissard Cécile Henry Stéphanie Blandin Pascal Richomme Olivier Coqueret Catherine Guette |
author_facet | Daniel L. Pouliquen Alice Boissard Cécile Henry Stéphanie Blandin Pascal Richomme Olivier Coqueret Catherine Guette |
author_sort | Daniel L. Pouliquen |
collection | DOAJ |
description | Investigations of liver metastatic colonization suggest that the microenvironment is preordained to be intrinsically hospitable to the invasive cancer cells. To identify molecular determinants of that organotropism and potential therapeutic targets, we conducted proteomic analyses of the liver in an aggressive model of sarcomatoid peritoneal mesothelioma (M5-T1). The quantitative changes between SWATH-MS (sequential window acquisition of all theoretical fragmentation spectra) proteotype patterns of the liver from normal rats (G1), adjacent non-tumorous liver from untreated tumor-bearing rats (G2), and liver from curcumin-treated rats without hepatic metastases (G3) were compared. The results identified 12 biomarkers of raised immune response against M5-T1 cells in G3 and 179 liver biomarker changes in (G2 vs. G1) and (G3 vs. G2) but not in (G3 vs. G1). Cross-comparing these 179 candidates with proteins showing abundance changes related to increasing invasiveness in four different rat mesothelioma tumor models identified seven biomarkers specific to the M5-T1 tumor. Finally, analysis of correlations between these seven biomarkers, purine nucleoside phosphorylase being the main biomarker of immune response, and the 179 previously identified proteins revealed a network orchestrating liver colonization and treatment efficacy. These results highlight the links between potential targets, raising interesting prospects for optimizing therapies against highly invasive cancer cells exhibiting a sarcomatoid phenotype and sarcoma cells. |
first_indexed | 2024-03-10T14:50:19Z |
format | Article |
id | doaj.art-f8ca79913e6e4b1c8034434df7a70332 |
institution | Directory Open Access Journal |
issn | 2072-6694 |
language | English |
last_indexed | 2024-03-10T14:50:19Z |
publishDate | 2020-11-01 |
publisher | MDPI AG |
record_format | Article |
series | Cancers |
spelling | doaj.art-f8ca79913e6e4b1c8034434df7a703322023-11-20T21:04:55ZengMDPI AGCancers2072-66942020-11-011211338410.3390/cancers12113384Curcumin Treatment Identifies Therapeutic Targets within Biomarkers of Liver Colonization by Highly Invasive Mesothelioma Cells—Potential Links with SarcomasDaniel L. Pouliquen0Alice Boissard1Cécile Henry2Stéphanie Blandin3Pascal Richomme4Olivier Coqueret5Catherine Guette6Université d’Angers, Inserm, CRCINA, F-44000 Nantes, FranceUniversité d’Angers, ICO Cancer Center, Inserm, CRCINA, F-44000 Nantes, FranceUniversité d’Angers, ICO Cancer Center, Inserm, CRCINA, F-44000 Nantes, FranceUniversité de Nantes, Plate-forme MicroPICell, SFR François Bonamy, F-44000 Nantes, FranceUniversité d’Angers, SONAS, EA921, SFR QUASAV, F-49000 Angers, FranceUniversité d’Angers, Inserm, CRCINA, F-44000 Nantes, FranceUniversité d’Angers, ICO Cancer Center, Inserm, CRCINA, F-44000 Nantes, FranceInvestigations of liver metastatic colonization suggest that the microenvironment is preordained to be intrinsically hospitable to the invasive cancer cells. To identify molecular determinants of that organotropism and potential therapeutic targets, we conducted proteomic analyses of the liver in an aggressive model of sarcomatoid peritoneal mesothelioma (M5-T1). The quantitative changes between SWATH-MS (sequential window acquisition of all theoretical fragmentation spectra) proteotype patterns of the liver from normal rats (G1), adjacent non-tumorous liver from untreated tumor-bearing rats (G2), and liver from curcumin-treated rats without hepatic metastases (G3) were compared. The results identified 12 biomarkers of raised immune response against M5-T1 cells in G3 and 179 liver biomarker changes in (G2 vs. G1) and (G3 vs. G2) but not in (G3 vs. G1). Cross-comparing these 179 candidates with proteins showing abundance changes related to increasing invasiveness in four different rat mesothelioma tumor models identified seven biomarkers specific to the M5-T1 tumor. Finally, analysis of correlations between these seven biomarkers, purine nucleoside phosphorylase being the main biomarker of immune response, and the 179 previously identified proteins revealed a network orchestrating liver colonization and treatment efficacy. These results highlight the links between potential targets, raising interesting prospects for optimizing therapies against highly invasive cancer cells exhibiting a sarcomatoid phenotype and sarcoma cells.https://www.mdpi.com/2072-6694/12/11/3384metastatic tumor cellssarcomatoid phenotypemalignant mesotheliomaproteomicsbiomarkersinvasiveness |
spellingShingle | Daniel L. Pouliquen Alice Boissard Cécile Henry Stéphanie Blandin Pascal Richomme Olivier Coqueret Catherine Guette Curcumin Treatment Identifies Therapeutic Targets within Biomarkers of Liver Colonization by Highly Invasive Mesothelioma Cells—Potential Links with Sarcomas Cancers metastatic tumor cells sarcomatoid phenotype malignant mesothelioma proteomics biomarkers invasiveness |
title | Curcumin Treatment Identifies Therapeutic Targets within Biomarkers of Liver Colonization by Highly Invasive Mesothelioma Cells—Potential Links with Sarcomas |
title_full | Curcumin Treatment Identifies Therapeutic Targets within Biomarkers of Liver Colonization by Highly Invasive Mesothelioma Cells—Potential Links with Sarcomas |
title_fullStr | Curcumin Treatment Identifies Therapeutic Targets within Biomarkers of Liver Colonization by Highly Invasive Mesothelioma Cells—Potential Links with Sarcomas |
title_full_unstemmed | Curcumin Treatment Identifies Therapeutic Targets within Biomarkers of Liver Colonization by Highly Invasive Mesothelioma Cells—Potential Links with Sarcomas |
title_short | Curcumin Treatment Identifies Therapeutic Targets within Biomarkers of Liver Colonization by Highly Invasive Mesothelioma Cells—Potential Links with Sarcomas |
title_sort | curcumin treatment identifies therapeutic targets within biomarkers of liver colonization by highly invasive mesothelioma cells potential links with sarcomas |
topic | metastatic tumor cells sarcomatoid phenotype malignant mesothelioma proteomics biomarkers invasiveness |
url | https://www.mdpi.com/2072-6694/12/11/3384 |
work_keys_str_mv | AT daniellpouliquen curcumintreatmentidentifiestherapeutictargetswithinbiomarkersoflivercolonizationbyhighlyinvasivemesotheliomacellspotentiallinkswithsarcomas AT aliceboissard curcumintreatmentidentifiestherapeutictargetswithinbiomarkersoflivercolonizationbyhighlyinvasivemesotheliomacellspotentiallinkswithsarcomas AT cecilehenry curcumintreatmentidentifiestherapeutictargetswithinbiomarkersoflivercolonizationbyhighlyinvasivemesotheliomacellspotentiallinkswithsarcomas AT stephanieblandin curcumintreatmentidentifiestherapeutictargetswithinbiomarkersoflivercolonizationbyhighlyinvasivemesotheliomacellspotentiallinkswithsarcomas AT pascalrichomme curcumintreatmentidentifiestherapeutictargetswithinbiomarkersoflivercolonizationbyhighlyinvasivemesotheliomacellspotentiallinkswithsarcomas AT oliviercoqueret curcumintreatmentidentifiestherapeutictargetswithinbiomarkersoflivercolonizationbyhighlyinvasivemesotheliomacellspotentiallinkswithsarcomas AT catherineguette curcumintreatmentidentifiestherapeutictargetswithinbiomarkersoflivercolonizationbyhighlyinvasivemesotheliomacellspotentiallinkswithsarcomas |