ArticleCell death & disease2023
Intratumor heterogeneity and cell secretome promote chemotherapy resistance and progression of colorectal cancer.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 25 citations in OpenAlex.
- An integrated spatially defined roadmap of normal and cancer-associated colon fibroblasts.Molecular systems biology · 2026Article
- Sphingolipid Remodeling in Colorectal Cancer Reveals a Continuum-like Metabolic Organization.Antioxidants (Basel, Switzerland) · 2026Article
- From 2D to 3D Colorectal Cancer Patient-Derived Organoids (PDOs) and In Vivo Models: Copper(II) Complexes as Promising New Antitumor Agents.Journal of medicinal chemistry · 2026Article
- Mitochondrial metabolism determines chemotherapy sensitivity in colorectal cancer.Nature metabolism · 2026Article
- Dormancy in Metastatic Colorectal Cancer: Tissue Engineering Opportunities forTissue engineering. Part B, Reviews · 2026Review
- Review
- Modulating the tumor immune phenotypes by radiotherapy: formulating and validating the combination therapy of radiation, PD-L1, and TIM-3 blockade in colorectal cancer.Journal for immunotherapy of cancer · 2026Article
- Liposomal Delivery of Pyronaridine as a Repurposed Inhibitor of ERCC1/XPF for the Sensitization of Colorectal Cancer Cells to Platinum Chemotherapeutics.Molecular pharmaceutics · 2026Article
- Strength through diversity: how cancers thrive when clones cooperate.Molecular oncology · 2026Review
- A single-cell derived spheroid approach to dissect intratumoural heterogeneity in colorectal cancer: cell lines show changes in proteomes and therapeutic response to 5-FU.Journal of cancer research and clinical oncology · 2026Article
- Comprehensive Landscape of Diagnostic, Prognostic and Predictive Biomarkers in Colorectal Cancer: From Genomics to Multi-Omics Integration in Precision Medicine.Journal of personalized medicine · 2026Review
- EphA2 sustains the adaptive response of colorectal organoids to chemotherapy.Frontiers in cell and developmental biology · 2026Article
- OT17 a novel microsatellite stable colorectal cancer cell line and organoid model for investigatingBiochemistry and biophysics reports · 2025Article
- Integrated Transcriptomic and Metabolomic Analysis Revealed That Tryptophan Metabolism-Related Metabolites Are Biomarkers of Trastuzumab Resistance.Journal of clinical laboratory analysis · 2025Article
- Development of a prognostic risk model for colorectal cancer based on microsatellite stability-associated genes.BMC cancer · 2025Article
- The aggressive colorectal cancer subtype marker HTR2B has a dual role depending on the tumor microenvironment.Cell communication and signaling : CCS · 2025Article
- Machine learning integration of single-cell and bulk transcriptomics identifies fibroblast-driven prognostic markers in colorectal cancer.Biomolecules & biomedicine · 2025Article
- Tumor secretome shapes the immune landscape during cancer progression.Journal of experimental & clinical cancer research : CR · 2025Review
- Mitigating the Oncogenic Roles of miR-629-5p and miR-660-5p Through Direct Binding by Two Potential Drug Targets for Colorectal Cancer Prevention.International journal of preventive medicine · 2025Article
- Self-assembled PROTACs enable protein degradation to reprogram the tumor microenvironment for synergistically enhanced colorectal cancer immunotherapy.Bioactive materials · 2025Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The major underlying cause for the high mortality rate in colorectal cancer (CRC) relies on its drug resistance, to which intratumor heterogeneity (ITH) contributes substantially. CRC tumors have been reported to comprise heterogeneous populations of cancer cells that can be grouped into 4 consensus molecular subtypes (CMS). However, the impact of inter-cellular interaction between these cellular states on the emergence of drug resistance and CRC progression remains elusive. Here, we explored the interaction between cell lines belonging to the CMS1 (HCT116 and LoVo) and the CMS4 (SW620 and MDST8) in a 3D coculture model, mimicking the ITH of CRC. The spatial distribution of each cell population showed that CMS1 cells had a preference to grow in the center of cocultured spheroids, while CMS4 cells localized at the periphery, in line with observations in tumors from CRC patients. Cocultures of CMS1 and CMS4 cells did not alter cell growth, but significantly sustained the survival of both CMS1 and CMS4 cells in response to the front-line chemotherapeutic agent 5-fluorouracil (5-FU). Mechanistically, the secretome of CMS1 cells exhibited a remarkable protective effect for CMS4 cells against 5-FU treatment, while promoting cellular invasion. Secreted metabolites may be responsible for these effects, as demonstrated by the existence of 5-FU induced metabolomic shifts, as well as by the experimental transfer of the metabolome between CMS1 and CMS4 cells. Overall, our results suggest that the interplay between CMS1 and CMS4 cells stimulates CRC progression and reduces the efficacy of chemotherapy.
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