ArticleBlood1999
Cell adhesion mediated drug resistance (CAM-DR): role of integrins and resistance to apoptosis in human myeloma cell lines.
Article in Blood, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 362 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
362 citing papers in PubMed, 1 synthesis or guideline pooled it, 860 citations in OpenAlex.
- Microfluidics and organ-on-a-chip technologies: A systematic review of the methods used to mimic bone marrow.PloS one · 2020Pooled it
- Enhancing the R-ISS classification of newly diagnosed multiple myeloma by quantifying circulating clonal plasma cells.American journal of hematology · 2020Trial
- Proteomic characterization of circulating extracellular vesicles identifies novel serum myeloma associated markers.Journal of proteomics · 2016Trial
- A niche-like culture system allowing the maintenance of primary human acute myeloid leukemia-initiating cells: a new tool to decipher their chemoresistance and self-renewal mechanisms.Stem cells translational medicine · 2014Trial
- Beyond DNA damage: 3D tumor models and the integrin mechanobiology of radioresistance.Journal of experimental & clinical cancer research : CR · 2026Review
- Review
- DLBCL-microenvironment interactions: cytokine profiling and ECM-mediated ibrutinib resistance in a 3D bone-based model.Medical oncology (Northwood, London, England) · 2026Article
- The Shape-Shifting Myeloma: Adaptive Plasticity as a Hallmark of Relapse and Refractoriness.Cancers · 2026Review
- Is there a link between fascia and cancer? From potential mechanisms to future treatment options.Frontiers in physiology · 2026Review
- Investigating the functions and molecular mechanisms of DTX3L in cancer progression.Frontiers in oncology · 2026Review
- Integrin-linked kinase (ILK) in hematologic malignancies: Bridging molecular mechanisms to therapeutic innovation.BioImpacts : BI · 2026Review
- A 3D engineered multiple myeloma niche for evaluating CAR T cell therapy.Frontiers in bioengineering and biotechnology · 2026Article
- B cell mechanobiology in health and disease: emerging techniques and insights into therapeutic responses.FEBS letters · 2025Review
- Targeting Integrin α2 to Overcome Imatinib Resistance in Chronic Myeloid Leukemia Cells.Biomolecules · 2025Article
- Integrins in Cancer Drug Resistance: Molecular Mechanisms and Clinical Implications.International journal of molecular sciences · 2025Review
- Integrating Tumor and Organoid DNA Methylation Profiles Reveals Robust Predictors of Chemotherapy Response in Rectal Cancer.medRxiv : the preprint server for health sciences · 2025Article
- Decellularized Cell-Secreted Extracellular Matrices as Biomaterials for Tissue Engineering.Small science · 2025Review
- Article
- Exosomal integrins in tumor progression, treatment and clinical prediction (Review).International journal of oncology · 2024Review
- Integrin mechanosensing relies on a pivot-clip mechanism to reinforce cell adhesion.Biophysical journal · 2024Article
302 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Integrin-mediated adhesion influences cell survival and may prevent programmed cell death. Little is known about how drug-sensitive tumor cell lines survive initial exposures to cytotoxic drugs and eventually select for drug-resistant populations. Factors that allow for cell survival following acute cytotoxic drug exposure may differ from drug resistance mechanisms selected for by chronic drug exposure. We show here that drug-sensitive 8226 human myeloma cells, demonstrated to express both VLA-4 (alpha4beta1) and VLA-5 (alpha5beta1) integrin fibronectin (FN) receptors, are relatively resistant to the apoptotic effects of doxorubicin and melphalan when pre-adhered to FN and compared with cells grown in suspension. This cell adhesion mediated drug resistance, or CAM-DR, was not due to reduced drug accumulation or upregulation of anti-apoptotic Bcl-2 family members. As determined by flow cytometry, myeloma cell lines selected for drug resistance, with either doxorubicin or melphalan, overexpress VLA-4. Functional assays revealed a significant increase in alpha4-mediated cell adhesion in both drug-resistant variants compared with the drug-sensitive parent line. When removed from selection pressure, drug-resistant cell lines reverted to a drug sensitive and alpha4-low phenotype. Whether VLA-4-mediated FN adhesion offers a survival advantage over VLA-5-mediated adhesion remains to be determined. In conclusion, we have demonstrated that FN-mediated adhesion confers a survival advantage for myeloma cells acutely exposed to cytotoxic drugs by inhibiting drug-induced apoptosis. This finding may explain how some cells survive initial drug exposure and eventually express classical mechanisms of drug resistance such as MDR1 overexpression.
Indexed as
Identifiers
10029595PMC5550098W1528751727What OpenQuestion holds
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.