ArticleCell adhesion & migration2017
Proteolytic fragments of fibronectin function as matrikines driving the chemotactic affinity of prostate cancer cells to human bone marrow mesenchymal stromal cells via the α5β1 integrin.
Article in Cell adhesion & migration, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Biomarkers of tumor invasiveness in proteomics (Review).International journal of oncology · 2020Pooled it
- An update on the landscape of collagen bioactive fragments.The FEBS journal · 2026Review
- Review
- A Novel Bispecific Integrin α5β1/αv Antibody Reprograms the Myc-Regulated Basal Phenotype of Prostate Cancer with NK Cell-Mediated Tumor Elimination.Molecular cancer research : MCR · 2025Article
- Role and mechanism of Integrin α5β1 in bone formation and disease.Frontiers in cell and developmental biology · 2025Review
- Relaxation of mucosal fibronectin fibers in late gut inflammation following neutrophil infiltration in mice.npj biological physics and mechanics · 2025Article
- The Potential of Extracellular Matrix- and Integrin Adhesion Complex-Related Molecules for Prostate Cancer Biomarker Discovery.Biomedicines · 2023Review
- Redox-active endosomes mediate α5β1 integrin signaling and promote chondrocyte matrix metalloproteinase production in osteoarthritis.Science signaling · 2023Article
- The role of integrin family in bone metabolism and tumor bone metastasis.Cell death discovery · 2023Review
- Targeting integrin α5β1 in urological tumors: opportunities and challenges.Frontiers in oncology · 2023Review
- Noncanonical Wnt/Ror2 signaling regulates cell-matrix adhesion to prompt directional tumor cell invasion in breast cancer.Molecular biology of the cell · 2022Article
- Review
- The role of Trop2 in prostate cancer: an oncogene, biomarker, and therapeutic target.American journal of clinical and experimental urology · 2021Article
- Hold on or Cut? Integrin- and MMP-Mediated Cell-Matrix Interactions in the Tumor Microenvironment.International journal of molecular sciences · 2020Review
- Downregulation of LINC00707 promotes osteogenic differentiation of human bone marrow‑derived mesenchymal stem cells by regulating DKK1 via targeting miR‑103a‑3p.International journal of molecular medicine · 2020Article
- Aberrant integrin αv and α5 expression in prostate adenocarcinomas and bone-metastases is consistent with a bone-colonizing phenotype.Translational andrology and urology · 2020Article
- S100A9 promotes prostate cancer cell invasion by activating TLR4/NF-κB/integrin β1/FAK signaling.OncoTargets and therapy · 2020Article
- The extracellular matrix in tumor progression and metastasis.Clinical & experimental metastasis · 2019Review
- Downregulation of NEAT1 reverses the radioactive iodine resistance of papillary thyroid carcinoma cell via miR-101-3p/FN1/PI3K-AKT signaling pathway.Cell cycle (Georgetown, Tex.) · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The haematopoietic niche is contributed to by bone marrow-resident mesenchymal stromal cells (BM-MSCs) and subverted by prostate cancer cells. To study mechanisms by which BM-MSCs and prostate cancer cells may interact, we assessed the migration, invasion, adhesion and proliferation of bone-derived prostate cancer cells (PC-3) in co-culture with pluripotent human BM-MSCs. We observed a strong adhesive, migratory and invasive phenotype of PC-3 cells with BM- MSC-co-culture and set out to isolate and characterize the bioactive principle. Initial studies indicated that chemotaxis was secondary to a protein residing in the >100kDa fraction. Size-exclusion chromatography (SEC) recovered peak activity in a high-molecular weight fraction containing thrombospondin-1 (TSP1). While TSP1 immunodepletion decreased activity, put-back with purified TSP1 did not reproduce bioactivity. Further purification of the TSP1-containing high-molecular weight fraction of the BM-MSC secretome with heparin-affinity chromatography recovered bioactivity with highly restricted bands on polyacrylamide gel electrophoresis, determined by mass spectroscopy to be proteolytic fragments of fibronectin (FN). Put-back experiments with full-length FN permitted adhesion but failed to induce migration. Monospecific antibodies to FN blocked adhesion. Proteolytic cleavage of FN generated FN fragments which now induced migration. Neutralizing monoclonal antibodies to FN receptors α5 and β1 integrins, and α5 knockdown specifically blocked migration and adhesion.
conclusionFibronectin fragments (FNFr) function as matrikines driving the chemotactic affinity of prostate cancer cells via the α5β1 integrin. Taken together with the high-frequency of α5β1 expression in disseminated prostate cancer cells in bone marrow aspirates from patients, the FNFr/FN-α5β1 interaction warrants further study as a therapeutic target.
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