ArticleProceedings of the National Academy of Sciences of the United States of America2014
Cellular heterogeneity profiling by hyaluronan probes reveals an invasive but slow-growing breast tumor subset.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 70 citations in OpenAlex.
- CD44-downregulation in multiple myeloma inhibits cytoskeleton rearrangement through actin depolymerization.Clinical and experimental medicine · 2025Article
- Identification of CD44 as a key engager to hyaluronic acid-rich extracellular matrices for cell traction force generation and tumor invasion in 3D.Matrix biology : journal of the International Society for Matrix Biology · 2025Article
- Hyaluronic Acid as a Modern Approach in Anticancer Therapy-Review.International journal of molecular sciences · 2022Review
- The 3D in vivo chorioallantoic membrane model and its role in breast cancer research.Journal of cancer research and clinical oncology · 2022Review
- Article
- In vivo growth of subclones derived from Lewis lung carcinoma is determined by the tumor microenvironment.American journal of cancer research · 2022Article
- Monitoring non-small cell lung cancer progression and treatment response through hyaluronic acid in sputum.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2022Article
- Targeting the extracellular matrix for immunomodulation: applications in drug delivery and cell therapies.Drug delivery and translational research · 2021Review
- Hyaluronan Functions in Wound Repair That Are Captured to Fuel Breast Cancer Progression.Biomolecules · 2021Review
- RHAMM Is a Multifunctional Protein That Regulates Cancer Progression.International journal of molecular sciences · 2021Review
- Protein Ligands in the Secretome of CD36Cancers · 2021Article
- CD44 activation state regulated by the CD44v10 isoform determines breast cancer proliferation.Oncology reports · 2021Article
- Hyaluronic Acid-Targeted Stimuli-Sensitive Nanomicelles Co-Encapsulating Paclitaxel and Ritonavir to Overcome Multi-Drug Resistance in Metastatic Breast Cancer and Triple-Negative Breast Cancer Cells.International journal of molecular sciences · 2021Article
- Identification of the HMMR Gene as a Diagnostic and Prognostic Biomarker in Hepatocellular Carcinoma Based on Integrated Bioinformatics Analysis.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Remodelling of the bone marrow microenvironment by stromal hyaluronan modulates the malignancy of breast cancer cells.Cell communication and signaling : CCS · 2020Article
- Isoform-specific promotion of breast cancer tumorigenicity by TBX3 involves induction of angiogenesis.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- Cell Adhesiveness Serves as a Biophysical Marker for Metastatic Potential.Cancer research · 2020Article
- Acquisition of a side population fraction augments malignant phenotype in ovarian cancer.Scientific reports · 2019Article
- A Robust 8-Gene Prognostic Signature for Early-Stage Non-small Cell Lung Cancer.Frontiers in oncology · 2019Article
- Dissecting the Dual Nature of Hyaluronan in the Tumor Microenvironment.Frontiers in immunology · 2019Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Tumor heterogeneity confounds cancer diagnosis and the outcome of therapy, necessitating analysis of tumor cell subsets within the tumor mass. Elevated expression of hyaluronan (HA) and HA receptors, receptor for HA-mediated motility (RHAMM)/HA-mediated motility receptor and cluster designation 44 (CD44), in breast tumors correlates with poor outcome. We hypothesized that a probe for detecting HA-HA receptor interactions may reveal breast cancer (BCa) cell heterogeneity relevant to tumor progression. A fluorescent HA (F-HA) probe containing a mixture of polymer sizes typical of tumor microenvironments (10-480 kDa), multiplexed profiling, and flow cytometry were used to monitor HA binding to BCa cell lines of different molecular subtypes. Formulae were developed to quantify binding heterogeneity and to measure invasion in vivo. Two subsets exhibiting differential binding (HA(-/low) vs. HA(high)) were isolated and characterized for morphology, growth, and invasion in culture and as xenografts in vivo. F-HA-binding amounts and degree of heterogeneity varied with BCa subtype, were highest in the malignant basal-like cell lines, and decreased upon reversion to a nonmalignant phenotype. Binding amounts correlated with CD44 and RHAMM displayed but binding heterogeneity appeared to arise from a differential ability of HA receptor-positive subpopulations to interact with F-HA. HA(high) subpopulations exhibited significantly higher local invasion and lung micrometastases but, unexpectedly, lower proliferation than either unsorted parental cells or the HA(-/low) subpopulation. Querying F-HA binding to aggressive tumor cells reveals a previously undetected form of heterogeneity that predicts invasive/metastatic behavior and that may aid both early identification of cancer patients susceptible to metastasis, and detection/therapy of invasive BCa subpopulations.
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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.