ArticleOncogene2023
Mesenchymal stromal cells confer breast cancer doxorubicin resistance by producing hyaluronan.
Article in Oncogene, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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Who cites it
10 citing papers in PubMed, 10 citations in OpenAlex.
- Article
- Targeting the tumor microenvironment: a new strategy for natural products in breast cancer therapy.Natural products and bioprospecting · 2026Review
- Enzyme-mediated remodeling of the extracellular matrix and glycocalyx to enhance immunotherapy in solid tumors.Bioengineering & translational medicine · 2026Review
- Tumor-associated mesenchymal stem/stromal cells in tumor microenvironment and carcinogenesis.Experimental hematology & oncology · 2025Review
- Exploring the Potentials of Hyaluronic Acid-coated Polymeric Nanoparticles in Enhanced Cancer Treatment by Precision Drug Delivery, Tackling Drug Resistance, and Reshaping the Tumour Micro Environment.Current medicinal chemistry · 2025Review
- Prospects and Challenges of Different Delivery Systems in Breast Tumors Therapy.Breast cancer : basic and clinical research · 2025Review
- Hydrogel-based platforms for site-specific doxorubicin release in cancer therapy.Journal of translational medicine · 2024Review
- Hyaluronic acid metabolism and chemotherapy resistance: recent advances and therapeutic potential.Molecular oncology · 2024Review
- Deciphering Drug Resistance: Investigating the Emerging Role of Hyaluronan Metabolism and Signaling and Tumor Extracellular Matrix in Cancer Chemotherapy.International journal of molecular sciences · 2024Review
- COL5A1 promotes triple-negative breast cancer progression by activating tumor cell-macrophage crosstalk.Oncogene · 2024Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Chemotherapy resistance represents a major cause of therapeutic failure and mortality in cancer patients. Mesenchymal stromal cells (MSCs), an integral component of tumor microenvironment, are known to promote drug resistance. However, the detailed mechanisms remain to be elucidated. Here, we found that MSCs confer breast cancer resistance to doxorubicin by diminishing its intratumoral accumulation. Hyaluronan (HA), a major extracellular matrix (ECM) product of MSCs, was found to mediate the chemoresistant effect. The chemoresistant effect of MSCs was abrogated when hyaluronic acid synthase 2 (HAS2) was depleted or inhibited. Exogenous HA also protected tumor grafts from doxorubicin. Molecular dynamics simulation analysis indicates that HA can bind with doxorubicin, mainly via hydrophobic and hydrogen bonds, and thus reduce its entry into breast cancer cells. This mechanism is distinct from the reported chemoresistant effect of HA via its receptor on cell surface. High HA serum levels were also found to be positively associated with chemoresistance in breast cancer patients. Our findings indicate that the HA-doxorubicin binding dynamics can confer cancer cells chemoresistance. Reducing HA may enhance chemotherapy efficacy.
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Registered trials
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.