ArticleScientific reports2015
Physical Intimacy of Breast Cancer Cells with Mesenchymal Stem Cells Elicits Trastuzumab Resistance through Src Activation.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 49 citations in OpenAlex.
- Therapeutic Extracellular Vesicles from Synovial Fibroblast-Primed MSCs for Osteoarthritis Treatment.Advanced healthcare materials · 2026Article
- The role of genetics and epigenetics in breast cancer: A comprehensive review of metastasis, risk factors, and future perspectives.Journal of pharmaceutical analysis · 2025Review
- The cellular composition of the tumor microenvironment is an important marker for predicting therapeutic efficacy in breast cancer.Frontiers in immunology · 2024Review
- A hybrid breast cancer/mesenchymal stem cell population enhances chemoresistance and metastasis.JCI insight · 2023Article
- Fibroblasts as Turned Agents in Cancer Progression.Cancers · 2023Review
- Investigating the Effects of Indirect Coculture of Human Mesenchymal Stem Cells on the Migration of Breast Cancer Cells: A Systematic Review and Meta-Analysis.Breast cancer : basic and clinical research · 2023Review
- Carcinoma-Associated Mesenchymal Stem/Stromal Cells: Architects of the Pro-tumorigenic Tumor Microenvironment.Stem cells (Dayton, Ohio) · 2022Review
- TA-MSCs, TA-MSCs-EVs, MIF: their crosstalk in immunosuppressive tumor microenvironment.Journal of translational medicine · 2022Review
- Cancer Stem Cells and Their Possible Implications in Cervical Cancer: A Short Review.International journal of molecular sciences · 2022Review
- Drug resistance in cancer therapy: the Pandora's Box of cancer stem cells.Stem cell research & therapy · 2022Review
- Article
- The role of mesenchymal stem cells in the occurrence, development, and therapy of hepatocellular carcinoma.Cancer medicine · 2022Review
- Mesenchymal stem cells in cancer therapy; the art of harnessing a foe to a friend.Iranian journal of basic medical sciences · 2021Review
- Effect of Breast Cancer and Adjuvant Therapy on Adipose-Derived Stromal Cells: Implications for the Role of ADSCs in Regenerative Strategies for Breast Reconstruction.Stem cell reviews and reports · 2021Review
- The root cause of drug resistance in HER2-positive breast cancer and the therapeutic approaches to overcoming the resistance.Pharmacology & therapeutics · 2021Review
- Wnt/β‑catenin signaling: Causes and treatment targets of drug resistance in colorectal cancer (Review).Molecular medicine reports · 2021Review
- Tumor microenvironment promotes breast cancer chemoresistance.Cancer chemotherapy and pharmacology · 2021Review
- Mesenchymal stem/stromal cells: Developmental origin, tumorigenesis and translational cancer therapeutics.Translational oncology · 2021Review
- Organotypic Models in Drug Development "Tumor Models and Cancer Systems Biology for the Investigation of Anticancer Drugs and Resistance Development".Handbook of experimental pharmacology · 2021Article
- Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of resistance to trastuzumab is a major obstacle for lasting effective treatment of patients with ErbB2-overexpressing tumors. Here, we demonstrate that the physical contact of breast cancer cells with mesenchymal stem cells (MSCs) is a potential modulator of trastuzumab response by activation of nonreceptor tyrosine kinase c-Src and down regulation of phosphatase and tensin homolog (PTEN). Using an in vitro patterned breast cancer/MSC co-culture model, we find that the presence of MSCs results in Src activation that is missing in cancer cells monoculture, transwell co-culture, and cells treated with MSCs conditioned media. Interestingly, the co-culture model also results in PTEN loss and activation of PI3K/AKT pathway that has been demonstrated as fundamental proliferative and survival pathways in clinical settings. To our knowledge, this is the first report that showed PTEN loss without the use of chemical inhibitors, matrix stiffness, or silencing RNAs. In addition, breast cancer cells in co-culture with MSCs conferred trastuzumab resistance in vitro as observed in the lack of inhibition of proliferative and migrative properties of the cancer cells. Our findings show that MSCs are potent mediators of resistance to trastuzumab and might reveal targets to enhance trastuzumab efficacy in patients.
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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.