Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cancer cells enter an adaptive persistence to survive radiotherapy and repopulate tumor 2

ABSTRACT: Tumor cell repopulation represents a critical factor in the failure of radiotherapy. Analogous to the concept of “drug-tolerant persistence (DTP)” in stress of chemo- or targeted therapy, here, we show that cancer cells enter a “radiation-tolerant persistence (RTP)” to survive radiotherapy and repopulate tumor. These RTP cells exhibit a distinct phenotype characterized by enlargement of cell sizes and nucleus, complex karyotype, cell cycle arrest and engagement of quiescence. A fraction of RTPs unexpectedly give birth to mitotic-competent progeny cells via a viral budding-mimicking cell division. To gain insight into the molecular mechanisms how RTPs generating progenies and repopulating tumors, we applied single cell SMART RNA-sequencing and 10x RNA-sequencing to different status of human colorectal cancer cells HCT116 before and exposed to irradiation. For the first time, we profiled two transitional transcriptional waves throughout budding process and characterized two gene panels associated with budding of RTPs, illustrating the therapeutic potential for blocking tumor repopulation after radiation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE221171 | GEO | 2023/01/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Cancer cells enter an adaptive persistence to survive radiotherapy and repopulate tumor 1

Project description:Tumor cell repopulation represents a critical factor in the failure of radiotherapy. Analogous to the concept of “drug-tolerant persistence (DTP)” in stress of chemo- or targeted therapy, here, we show that cancer cells enter a “radiation-tolerant persistence (RTP)” to survive radiotherapy and repopulate tumor. These RTP cells exhibit a distinct phenotype characterized by enlargement of cell sizes and nucleus, complex karyotype, cell cycle arrest and engagement of quiescence. A fraction of RTPs unexpectedly give birth to mitotic-competent progeny cells via a viral budding-mimicking cell division. To gain insight into the molecular mechanisms how RTPs generating progenies and repopulating tumors, we applied single cell SMART RNA-sequencing and 10x RNA-sequencing to different status of human colorectal cancer cells HCT116 before and exposed to irradiation. For the first time, we profiled two transitional transcriptional waves throughout budding process and characterized two gene panels associated with budding of RTPs, illustrating the therapeutic potential for blocking tumor repopulation after radiation.

2023-01-06 | GSE221180 | GEO

Expression data from human esophageal cancer cells

Project description:When esophageal cancer cells are exposed to a certain dose of radiation, a series of biological process changes, including DNA damage, DNA repair, apoptosis, cell cycle, repopulation, mitotic disasters, etc. These changes may determine the radiotherapy sensitivity to esophageal cancer, as well as recurrence and metastasis after radiotherapy. To clarify the changes in gene expression in esophageal cancer after radiotherapy, we used gene expression microarrays to screen for significant up-regulation and down-regulation of genes and to analyze associations with these biological processes.

2019-10-01 | GSE138162 | GEO

Colorectal cancer cells possess an equipotent capacity to enter a reversible diapause-like state to survive chemotherapy

Project description:Cancer cells enter a reversible drug tolerant persister (DTP) state to evade death from chemotherapies and targeted agents. It is increasingly appreciated that DTPs are an important driver of therapy failure and tumor relapse. We combined cellular barcoding and mathematical modeling in patient-derived colorectal cancer models to identify and characterize DTPs in response to chemotherapy. Barcode analysis revealed no loss in clonal complexity of tumors that entered the DTP state and recurred following treatment cessation. Our data fits a mathematical model where all cancer cells, and not a small subpopulation, possess an equipotent capacity to become DTPs. Mechanistically, we determined that DTPs display remarkable transcriptional and functional similarities to diapause, a reversible state of suspended embryonic development triggered by unfavorable environmental conditions. Our study provides insight into how cancer cells use a developmentally conserved mechanism to drive the DTP state pointing to novel therapeutic opportunities to target DTPs.

2021-01-07 | GSE145356 | GEO

Quantitative analysis of transcriptomes in irradiated/unirradiated pancreatic cancer cells

Project description:Irradiated dying tumor cells play crucial roles in tumor repopulation. However, the transcriptome changes in pancreatic cancer cells after radiation remains unknown. Here we performed RNA-sequencing in pancreatic cancer cell line SW1990 and PANC-1 that were 10Gy irradiated or unirradiated. Bioinformatic analysis revealed that the transcriptomes were significantly changed after radiation. Gene Ontology (GO) analysis revealed that the signaling concerning extracellular vesicles, especially exosomes, were significantly enriched. Further investigation revealed the vital role of irradiated dying tumor cells-derived exosomes in potentiating tumor repopulation.

2020-06-14 | GSE138984 | GEO

Investigating tumor radiation response heterogeneity using single-cell sequencing

Project description:Tumor cell radioresistance is a major challenge in radiotherapy. By contrast, radiation response heterogeneity of tumor cells is poorly understood. Here, we performed scRNA-seq and scATAC-seq of 6 Gy γ-ray treated human lung adenocarcinoma cells to dissect cellular radiation response heterogeneity from perspective of transcriptional and regulatory cell states. Notably, we observed heterogeneous radioresponsiveness in purified lung adenocarcinoma cells by qualified cellular radiation response based on transcriptional landscape. There was DNA repair and apoptosis related transcriptional cell state appeared post-irradiation. We identified gene markers in this radiation-associated cell state and screened promising targets for LUAD radiosensitization based on 107 transcriptomic data of radiotherapy treated LUAD patients from TCGA database. Besides, transcriptional cell states transition was obvious accompanied with radiation-induced cell cycle arrest in which cell-cell communication was a potential regulatory mechanism. Finally, we identified radiation-associated regulatory cell state and analyzed the regulatory network of key transcriptional factors in cellular radiation response.

2022-08-22 | GSE211617 | GEO

A novel approach for the discovery of biomarkers of radiotherapy response in breast cancer

Project description:Radiotherapy is a commonly used treatment modality for the local control of breast cancer. However, the clinical signs of radiotherapy response are often not apparent for several weeks post-treatment. We currently lack tools to predict and/or monitor tumor responses during treatment. The aim of this study was to identify tumor secreted biomarkers of radiotherapy response. Estrogen receptor positive (ER+) MCF-7 cells were serum-starved for 2 h, and were then exposed to various doses of radiation (0, 2, 4, 6, 8 or 10 Gy). Conditioned media (CM) was harvested at 1, 2, 4, 8 and 24 h post-radiation for each radiation dose. Samples underwent processing for liquid chromatography-mass spectrometry (LC-MS) following collection. 33 proteins at the 24 h time point were found to have significantly increased secretion levels (up to 12-fold) at all radiation doses compared to untreated cells. To validate the secretomic results and to further investigate the potential use of these proteins as biomarkers of radiosensitivity, the secreted protein levels of candidate biomarkers were assessed through western blot (WB). WB analysis was performed using CM samples to assess the secretion levels from parental and radioresistant (RR) cell lines (developed within our lab) 24 h after the cells had received a single radiation dose of 2 Gy. Secretion levels of our candidate biomarkers were found to be significantly increased from the radiosensitive MCF-7 cells treated with 2 Gy of radiation at 24 h compared to 24 h untreated controls. In comparison, candidate biomarker levels in the CM samples from untreated and radiation-treated MCF-7 RR cells remained low. Currently there are no validated predictive biomarkers to monitor radiotherapy responses during treatment. These biomarkers could have a clinical role in personalising radiotherapy dosing schedules and durations for solid tumours in the neoadjuvant and palliative setting.

2021-08-13 | PXD027572 | Pride

Gene expression profile of colorectal cancer HCT116 cells treated with single (2Gy) or fractionated (5 x 2Gy) doses of ionizing radiation.

Project description:Radiotherapy remains a standard treatment for colorectal cancer. The clinical significance of the conventional treatment is based on accumulated dose and usually consists of single daily irradiations of 1.8 - 2 Gy fractions. However the repopulation of cancer cells during and/or after the treatment suggests that the surviving fraction of cells acquire the radioresistance to cancer therapy. It has been determined a number of radioresistance markers, but only limited data exist on the acquisition of the resistance to fractionated radiation therapy. This research provides the genomic data of gene expression changes in colorectal cancer cell HCT116 line following single and multiple fractions of irradiation, aiming to identify particular genes associated with the effect of fractionated radiotherapy.

2017-08-29 | GSE103178 | GEO

TGFÎ² confers resistance to radiotherapy in non-small cell lung cancer

Project description:Radiotherapy is standard of care for inoperable non-small cell lung cancers (NSCLC) but adenocarcinoma NSCLC respond more poorly than squamous cell NSCLC. Transforming growth factor Î² (TGFÎ²) activity is induced by radiation and plays a recently recognized role in the DNA damage response. Here we show in murine lung tumor model that radiation activates TGFÎ² acutely and persistently and that TGFÎ² neutralizing antibody, 1D11, systemic treatment increased tumor control following either fractionated or single high dose radiation regimes. TGFÎ² dependent genes in the irradiated tumor indicated crosstalk between innate and adaptive immunity but therapeutic benefit of 1D11 in irradiated tumors in immunocompromised mice suggested that innate immune cells are more influential than the adaptive immune response. Irradiated tumors in which TGFÎ² was blocked were highly hypoxic, exhibit pronounced microvascular damage and promoted neither cancer-associated fibroblasts nor recruit bone marrow derived cells (BMDC). Tumor educated immature BMDC were significant sources of TGFÎ² and inhibiting BMDC recruitment achieved tumor growth control in response to RT comparable to TGFÎ² inhibition. Thus, radiation-induced TGFÎ² both compromises tumor control by RT and promotes reestablishment of the tumor microenvironment. Concordant with the critical role of TGFÎ² activity in RT, radiation resistant NSCLC adenocarcinomas exhibit higher TGFÎ² activity compared to squamous cell NSCLC, which suggests a rationale for using TGFÎ² inhibition to augment radiotherapy. Lewis lung cancer (LLC) model were established in 6 to 8 week-old C57BL/6 female mice by subcutaneous injection. When tumors were 60-80 mm3, Mice were randomized to achieve comparable mean tumor size for each treatment group as indicated below. Tumor growth were monitored and tumors were collected and characterized by gene expression profiling and immunostaining.

2015-12-15 | E-GEOD-73095 | biostudies-arrayexpress

Protein difference of breast cancer tissue in mice after radiation therapy and without radiation

Project description:In this study, radiation therapy was performed on mouse breast cancer spontaneous gene mice (MMTV-PyMT) to obtain radiation therapy model of breast cancer mice. To simulate clinical breast cancer radiotherapy and study the differential proteins of breast cancer radiotherapy resistance. MMTV-PyMT mice were randomly divided into two groups, and the radiotherapy group was given the same dose 5 times (3GY, once every 2 days) when the breast cancer tumor grew to an appropriate size (200mm3). The protein extracted from mouse tumor was analyzed by mass spectrometry.

2023-12-06 | PXD047555 | iProX

Colorectal Cancer Cells Enter a Diapause-like DTP State to Survive Chemotherapy.

Project description:Cancer cells enter a reversible drug-tolerant persister (DTP) state to evade death from chemotherapy and targeted agents. It is increasingly appreciated that DTPs are important drivers of therapy failure and tumor relapse. We combined cellular barcoding and mathematical modeling in patient-derived colorectal cancer models to identify and characterize DTPs in response to chemotherapy. Barcode analysis revealed no loss of clonal complexity of tumors that entered the DTP state and recurred following treatment cessation. Our data fit a mathematical model where all cancer cells, and not a small subpopulation, possess an equipotent capacity to become DTPs. Mechanistically, we determined that DTPs display remarkable transcriptional and functional similarities to diapause, a reversible state of suspended embryonic development triggered by unfavorable environmental conditions. Our study provides insight into how cancer cells use a developmentally conserved mechanism to drive the DTP state, pointing to novel therapeutic opportunities to target DTPs.

| S-EPMC8437243 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data