Radioresistance observed in patients with colorectal cancer (CRC) may be related to the presence of cancer stem cells (CSCs), but the underlying mechanism(s) remain unclear. Cancer-associated fibroblasts (CAFs) can regulate the stemness of cancer cells and tumor radiosensitivity. In addition, exosomes have been reported to modify treatment response by mediating cell-cell communication. In this study, we aimed to investigate whether exosomes derived from CAFs (CAF-exosomes) are involved in mediating resistance to radiotherapy in colorectal cancer and to explore the underlying mechanism. We found that CSCs were inherently resistant to cell death induced by radiotherapy. CAF-derived CM promoted clonogenicity and radioresistance of CRC cells. Further investigations revealed that exosomes isolated from CM induced the above effects whereas exosome-depleted CM (solution) was not able to induce clonogenicity and radioresistance. Finally, exosomes could activate transforming growth factor-β (TGF-β) signaling pathway and TGFβ1-neutralizing antibody inhibit this effect and decrease clonogenicity and expression levels of stemness genes. In conclusion,our findings suggest CAFs promote stemness of CRC cells and thus increase radiation resistance. Exosomes derived from CAFs play a crucial role through activating TGF-β signaling pathway in this process.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.yexcr.2020.111956 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Nano-delivery of a novel inhibitor of ERCC1-XPF for targeted sensitization of colorectal cancer to platinum-based chemotherapeutics.
Drug Deliv Transl Res
January 2025
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, T6G 2E1, Canada.
In this study, a novel inhibitor of ERCC1/XPF heterodimerization, A4, was used as an inhibitor of repair for DNA damage by platinum-based chemotherapeutics. Nano-formulations of A4 were developed, using self-assembly of the following block copolymers: methoxy-poly(ethylene oxide)-block-poly(α-benzyl carboxylate-ε-caprolactone) (PEO-b-PBCL), methoxy-poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-b-PCL), or methoxy-poly(ethylene oxide)-block-poly (D, L, lactide) (PEO-b-PDLA 50-50). The nano-formulations were characterized for their average diameter, polydispersity, morphology, A4 encapsulation and in vitro release.
View Article and Find Full Text PDFIntralesional injection of CpG ODNs complexed with glatiramer acetate mitigates systemic cytokine toxicities and synergistically advances checkpoint blockade efficacy.
Drug Deliv Transl Res
January 2025
Kinimmune, Inc. St. Louis, 63141, Missouri, USA.
PD-L1/PD-1 checkpoint inhibitors (CPIs) are mainstream agents for cancer immunotherapy, but the prognosis is unsatisfactory in solid tumor patients lacking preexisting T-cell reactivity. Adjunct therapy strategies including the intratumoral administration of immunostimulants aim to address this limitation. CpG oligodeoxynucleotides (ODNs), TLR9 agonists that can potentiate adaptive immunity, have been widely investigated to tackle PD-L1/PD-1 resistance, but clinical success has been hindered by inconsistent efficacy and immune-related toxicities caused by systemic exposure.
View Article and Find Full Text PDFGlobal prevalence and moderating factors of malnutrition in colorectal cancer survivors: A meta-analysis.
J Cancer Surviv
January 2025
School of Nursing, College of Nursing, Taipei Medical University, Taipei, Taiwan.
Purpose: This meta-analysis aims to estimate the global prevalence of severe, moderate, overall malnutrition and moderating factors of malnutrition in colorectal cancer (CRC) survivors.
Methods: A comprehensive search was conducted in Embase, CINAHL, Medline-OVID, PubMed, Scopus, and Web of Science from inception to February 8, 2024, without language, region, or publication date restrictions. A generalized linear mixed model and random-effects model were used to examine the pooled prevalence, and moderator analyses were implemented to investigate variations in the pooled prevalence.
Gold nanocomposites in colorectal cancer therapy: characterization, selective cytotoxicity, and migration inhibition.
Naunyn Schmiedebergs Arch Pharmacol
January 2025
Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, UCSI University, No. 1, Jalan Menara Gading, Taman Connaught, Cheras, Kuala Lumpur, 56000, Malaysia.
The third most prevalent type of cancer in the world, colorectal cancer, poses a significant treatment challenge due to the nonspecific distribution, low efficacy, and high systemic toxicity associated with chemotherapy. To overcome these limitations, a targeted drug delivery system with a high cytotoxicity against cancer cells while maintaining a minimal systemic side effects represents a promising therapeutic approach. Therefore, the aim of this study was to develop an efficient gold nanocarrier for the targeted delivery of the anticancer agent everolimus to Caco-2 cells.
View Article and Find Full Text PDFMonotropein represses the proliferation and angiogenesis via the AKT/NF-κB pathway in lung cancer.
Naunyn Schmiedebergs Arch Pharmacol
January 2025
General Hospital of Ningxia Medical University, Yinchuan, 750001, Ningxia, P. R. China.
Monotropein (Mon) is an iridoid glycosides extracted from Morinda officinalis F.C. How.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!