ArticleMolecular cancer2018
CCL2/CCL5 secreted by the stroma induce IL-6/PYK2 dependent chemoresistance in ovarian cancer.
Article in Molecular cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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52 citing papers in PubMed, 111 citations in OpenAlex.
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- Integrin αVβ1-activated PYK2 promotes the progression of non-small-cell lung cancer via the STAT3-VGF axis.Cell communication and signaling : CCS · 2024Article
- Targeting interleukin-6 as a treatment approach for peritoneal carcinomatosis.Journal of translational medicine · 2024Review
- Unveiling the prognostic significance of malignant ascites in advanced gastrointestinal cancers: a marker of peritoneal carcinomatosis burden.Therapeutic advances in medical oncology · 2024Article
- Article
- CC Chemokine 2 Promotes Ovarian Cancer Progression through the MEK/ERK/MAP3K19 Signaling Pathway.International journal of molecular sciences · 2023Article
- Mechanobiology of cancer cell responsiveness to chemotherapy and immunotherapy: Mechanistic insights and biomaterial platforms.Advanced drug delivery reviews · 2023Review
- The m6A methyltransferase METTL16 negatively regulates MCP1 expression in mesenchymal stem cells during monocyte recruitment.JCI insight · 2023Article
- Activated PyK2 and Its Associated Molecules Transduce Cellular Signaling from the Cancerous Milieu for Cancer Metastasis.International journal of molecular sciences · 2022Review
- Role of CC-chemokine ligand 2 in gynecological cancer.Cancer cell international · 2022Review
- Akt-Activated Endothelium Increases Cancer Cell Proliferation and Resistance to Treatment in Ovarian Cancer Cell Organoids.International journal of molecular sciences · 2022Article
- Integration of Genomic Biology Into Therapeutic Strategies of Gastric Cancer Peritoneal Metastasis.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022Review
- TA-MSCs, TA-MSCs-EVs, MIF: their crosstalk in immunosuppressive tumor microenvironment.Journal of translational medicine · 2022Review
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMinimal residual disease is the main issue of advanced ovarian cancer treatment. According to the literature and previous results, we hypothesized that Mesenchymal Stromal Cells (MSC) could support this minimal residual disease by protecting ovarian cancer cells (OCC) from chemotherapy. In vitro study confirmed that MSC could induce OCC chemoresistance without contact using transwell setting. Further experiments showed that this induced chemoresistance was dependent on IL-6 OCC stimulation.
methodsWe combined meticulous in vitro profiling and tumor xenograft models to study the role of IL-6 in MSC/OCC intereactions.
resultsWe demonstrated that Tocilizumab® (anti-IL-6R therapy) in association with chemotherapy significantly reduced the peritoneal carcinosis index (PCI) than chemotherapy alone in mice xenografted with OCCs+MSCs. Further experiments showed that CCL2 and CCL5 are released by MSC in transwell co-culture and induce OCCs IL-6 secretion and chemoresistance. Finally, we found that IL-6 induced chemoresistance was dependent on PYK2 phosphorylation.
conclusionsThese findings highlight the potential key role of the stroma in protecting minimal residual disease from chemotherapy, thus favoring recurrences. Future clinical trials targeting stroma could use anti-IL-6 therapy in association with chemotherapy.
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