ArticleThe Prostate2010
CCL2 is induced by chemotherapy and protects prostate cancer cells from docetaxel-induced cytotoxicity.
Article in The Prostate, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 112 citations in OpenAlex.
- Stromal CYR61 Confers Resistance to Mitoxantrone via Spleen Tyrosine Kinase Activation in Human Acute Myeloid Leukaemia.British journal of haematology · 2015Trial
- A feedback mechanism from prostate cancer cells to macrophages, reinforced by STAT1, regulates tumor progression and resistance to radiotherapy.Cell death & disease · 2026Article
- The immune landscape of systemic inflammation in prostate cancer.Cancer biology & medicine · 2025Review
- Menin in Cancer.Genes · 2024Review
- Feasibility of androgen-deprivation and radiation therapy with docetaxel for localized high-risk prostate cancer.Translational andrology and urology · 2024Article
- Targeting CCL2/CCR2 Signaling Overcomes MEK Inhibitor Resistance in Acute Myeloid Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- PD-1 inhibitor combined with Docetaxel exerts synergistic anti-prostate cancer effect in mice by down-regulating the expression of PI3K/AKT/NFKB-P65/PD-L1 signaling pathway.Cancer biomarkers : section A of Disease markers · 2024Article
- Investigation of enzalutamide, docetaxel, and cabazitaxel resistance in the castration resistant prostate cancer cell line C4 using genome-wide CRISPR/Cas9 screening.Scientific reports · 2023Article
- Current Developments in Cellular Therapy for Castration Resistant Prostate Cancer: A Systematic Review of Clinical Studies.Cancers · 2022Review
- Interplay between fat cells and immune cells in bone: Impact on malignant progression and therapeutic response.Pharmacology & therapeutics · 2022Review
- Serum CCL2 Is a Prognostic Biomarker for Non-Metastatic Castration-Sensitive Prostate Cancer.Biomedicines · 2022Article
- Review
- Immunotherapy by mesenchymal stromal cell delivery of oncolytic viruses for treating metastatic tumors.Molecular therapy oncolytics · 2022Review
- Comparative proteome analysis identified CD44 as a possible serum marker for docetaxel resistance in castration-resistant prostate cancer.Journal of cellular and molecular medicine · 2022Article
- Menin inhibition suppresses castration-resistant prostate cancer and enhances chemosensitivity.Oncogene · 2022Article
- Plasma Chemokine C-C Motif Ligand 2 as a Potential Biomarker for Prostate Cancer.Research and reports in urology · 2022Article
- Role of PI3K-AKT-mTOR Pathway as a Pro-Survival Signaling and Resistance-Mediating Mechanism to Therapy of Prostate Cancer.International journal of molecular sciences · 2021Review
- The potential of CAR T cell therapy for prostate cancer.Nature reviews. Urology · 2021Review
- The multifaceted roles of the chemokines CCL2 and CXCL12 in osteophilic metastatic cancers.Cancer metastasis reviews · 2021Review
- Macrophages expedite cell proliferation of prostate intraepithelial neoplasia through their downstream target ERK.The FEBS journal · 2021Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundMetastatic prostate cancer is either inherently resistant to chemotherapy or rapidly acquires this phenotype after chemotherapy exposure. In this study, we identified a docetaxel-induced resistance mechanism centered on CCL2.
methodsWe compared the gene expression profiles in individual human prostate cancer specimens before and after exposure to chemotherapy collected from previously untreated patients who participated in a clinical trial of preoperative chemotherapy. Subsequently, we used the gain- and loss-of-function approach in vitro to identify a potential mechanism underlying chemotherapy resistance.
resultsAmong the molecular signatures associated with treatment, several genes that regulate the inflammatory response and chemokine activity were upregulated including a significant increase in transcripts encoding the CC chemokine CCL2. Docetaxel increased CCL2 expression in prostate cancer cell lines in vitro. CCL2-specific siRNA inhibited LNCaP and LAPC4 cell proliferation and enhanced the growth inhibitory effect of low-dose docetaxel. In contrast, overexpression of CCL2 or recombinant CCL2 protein stimulated prostate cancer cell proliferation and rescued cells from docetaxel-induced cytotoxicity. This protective effect of CCL2 was associated with activation of the ERK/MAP kinase and PI3K/AKT, inhibition of docetaxel-induced Bcl2 phosphorylation at serine 70, phosphorylation of Bad, and activation of caspase-3. The addition of a PI3K/AKT inhibitor Ly294002 reversed the CCL2 protection and was additive to docetaxel-induced toxicity.
conclusionThese results support a mechanism of chemotherapy resistance mediated by cellular stress responses involving the induction of CCL2 expression and suggest that inhibiting CCL2 activity could enhance therapeutic responses to taxane-based therapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.