Distinct transcriptional programs in ascitic and solid cancer cells induce different responses to chemotherapy in high-grade serous ovarian cancer
- Author
- Nele Loret (UGent) , Niels Vandamme (UGent) , Jordy De Coninck (UGent) , Joachim Taminau (UGent) , Kato De Clercq (UGent) , Gillian Blancke (UGent) , Sven Jonckheere, Steven Goossens (UGent) , Kelly Lemeire (UGent) , Sofie De Prijck (UGent) , Kevin Verstaen (UGent) , Ruth Seurinck (UGent) , Jo Van Dorpe (UGent) , Steven Weyers (UGent) , Hannelore Denys (UGent) , Koen Van de Vijver (UGent) , Bart Lambrecht (UGent) , Philippe Tummers (UGent) , Yvan Saeys (UGent) and Geert Berx (UGent)
- Organization
- Project
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- De rol van ZEB transcriptiefactoren in kwaadaardige progressie en therapieresistentie in hooggradige sereuze ovariumcarcinomen
- ZENTACC: Targeting ZEB pathways to tackle aggressive (colorectal) cancer
- Targeting the Tumor Microenvironment in Colorectal Peritoneal Metastases
- Defining the role of ZEB1 in tumour initiation and progression of basal-like breast cancer
- Preclinical validation of novel plastistatic therapy for malignant colon cancer
- Abstract
- High-grade serous ovarian cancer (HGSOC) is responsible for the largest number of ovarian cancer deaths. The frequent therapy-resistant relapses necessitate a better understanding of mechanisms driving therapy resistance. Therefore, we mapped more than a hundred thousand cells of HGSOC patients in different phases of the disease, using single-cell RNA sequencing. Within patients, we compared chemonaive with chemotreated samples. As such, we were able to create a single-cell atlas of different HGSOC lesions and their treatment. This revealed a high intrapatient concordance between spatially distinct metastases. In addition, we found remarkable baseline differences in transcriptomics of ascitic and solid cancer cells, resulting in a different response to chemotherapy. Moreover, we discovered different robust subtypes of cancer-associated fibroblasts (CAF) in all patients. Besides inflammatory CAFs, vascular CAFs, and matrix CAFs, we identified a new CAF subtype that was characterized by high expression of STAR, TSPAN8, and ALDH1A1 and clearly enriched after chemotherapy. Together, tumor heterogeneity in both cancer and stromal cells contributes to therapy resistance in HGSOC and could form the basis of novel therapeutic strategies that differentiate between ascitic and solid disease.
- Keywords
- Cancer Research, Oncology, Molecular Biology, FALLOPIAN-TUBE, HETEROGENEITY, METASTASIS, EXPRESSION, TRAJECTORIES, FIBROBLASTS, EPITHELIUM
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8758523
- MLA
- Loret, Nele, et al. “Distinct Transcriptional Programs in Ascitic and Solid Cancer Cells Induce Different Responses to Chemotherapy in High-Grade Serous Ovarian Cancer.” MOLECULAR CANCER RESEARCH, vol. 20, no. 10, 2022, pp. 1532–47, doi:10.1158/1541-7786.mcr-21-0565.
- APA
- Loret, N., Vandamme, N., De Coninck, J., Taminau, J., De Clercq, K., Blancke, G., … Berx, G. (2022). Distinct transcriptional programs in ascitic and solid cancer cells induce different responses to chemotherapy in high-grade serous ovarian cancer. MOLECULAR CANCER RESEARCH, 20(10), 1532–1547. https://doi.org/10.1158/1541-7786.mcr-21-0565
- Chicago author-date
- Loret, Nele, Niels Vandamme, Jordy De Coninck, Joachim Taminau, Kato De Clercq, Gillian Blancke, Sven Jonckheere, et al. 2022. “Distinct Transcriptional Programs in Ascitic and Solid Cancer Cells Induce Different Responses to Chemotherapy in High-Grade Serous Ovarian Cancer.” MOLECULAR CANCER RESEARCH 20 (10): 1532–47. https://doi.org/10.1158/1541-7786.mcr-21-0565.
- Chicago author-date (all authors)
- Loret, Nele, Niels Vandamme, Jordy De Coninck, Joachim Taminau, Kato De Clercq, Gillian Blancke, Sven Jonckheere, Steven Goossens, Kelly Lemeire, Sofie De Prijck, Kevin Verstaen, Ruth Seurinck, Jo Van Dorpe, Steven Weyers, Hannelore Denys, Koen Van de Vijver, Bart Lambrecht, Philippe Tummers, Yvan Saeys, and Geert Berx. 2022. “Distinct Transcriptional Programs in Ascitic and Solid Cancer Cells Induce Different Responses to Chemotherapy in High-Grade Serous Ovarian Cancer.” MOLECULAR CANCER RESEARCH 20 (10): 1532–1547. doi:10.1158/1541-7786.mcr-21-0565.
- Vancouver
- 1.Loret N, Vandamme N, De Coninck J, Taminau J, De Clercq K, Blancke G, et al. Distinct transcriptional programs in ascitic and solid cancer cells induce different responses to chemotherapy in high-grade serous ovarian cancer. MOLECULAR CANCER RESEARCH. 2022;20(10):1532–47.
- IEEE
- [1]N. Loret et al., “Distinct transcriptional programs in ascitic and solid cancer cells induce different responses to chemotherapy in high-grade serous ovarian cancer,” MOLECULAR CANCER RESEARCH, vol. 20, no. 10, pp. 1532–1547, 2022.
@article{8758523,
abstract = {{High-grade serous ovarian cancer (HGSOC) is responsible for the largest number of ovarian cancer deaths. The frequent therapy-resistant relapses necessitate a better understanding of mechanisms driving therapy resistance. Therefore, we mapped more than a hundred thousand cells of HGSOC patients in different phases of the disease, using single-cell RNA sequencing. Within patients, we compared chemonaive with chemotreated samples. As such, we were able to create a single-cell atlas of different HGSOC lesions and their treatment. This revealed a high intrapatient concordance between spatially distinct metastases. In addition, we found remarkable baseline differences in transcriptomics of ascitic and solid cancer cells, resulting in a different response to chemotherapy. Moreover, we discovered different robust subtypes of cancer-associated fibroblasts (CAF) in all patients. Besides inflammatory CAFs, vascular CAFs, and matrix CAFs, we identified a new CAF subtype that was characterized by high expression of STAR, TSPAN8, and ALDH1A1 and clearly enriched after chemotherapy. Together, tumor heterogeneity in both cancer and stromal cells contributes to therapy resistance in HGSOC and could form the basis of novel therapeutic strategies that differentiate between ascitic and solid disease.}},
author = {{Loret, Nele and Vandamme, Niels and De Coninck, Jordy and Taminau, Joachim and De Clercq, Kato and Blancke, Gillian and Jonckheere, Sven and Goossens, Steven and Lemeire, Kelly and De Prijck, Sofie and Verstaen, Kevin and Seurinck, Ruth and Van Dorpe, Jo and Weyers, Steven and Denys, Hannelore and Van de Vijver, Koen and Lambrecht, Bart and Tummers, Philippe and Saeys, Yvan and Berx, Geert}},
issn = {{1541-7786}},
journal = {{MOLECULAR CANCER RESEARCH}},
keywords = {{Cancer Research,Oncology,Molecular Biology,FALLOPIAN-TUBE,HETEROGENEITY,METASTASIS,EXPRESSION,TRAJECTORIES,FIBROBLASTS,EPITHELIUM}},
language = {{eng}},
number = {{10}},
pages = {{1532--1547}},
title = {{Distinct transcriptional programs in ascitic and solid cancer cells induce different responses to chemotherapy in high-grade serous ovarian cancer}},
url = {{http://doi.org/10.1158/1541-7786.mcr-21-0565}},
volume = {{20}},
year = {{2022}},
}
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