ArticleOncotarget2016
Fibrotic microenvironment promotes the metastatic seeding of tumor cells via activating the fibronectin 1/secreted phosphoprotein 1-integrin signaling.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 48 citations in OpenAlex.
- Pulmonary fibrosis complicated by lung cancer: bibliometric analysis from 2004 to 2024 - research status, trends and future directions.Frontiers in immunology · 2025Pooled it
- High expression of SPP1 in patients with chronic obstructive pulmonary disease (COPD) is correlated with increased risk of lung cancer.FEBS open bio · 2021Pooled it
- FN1 as a key gene in modulating the integrin cell surface pathway in breast cancer.Medical oncology (Northwood, London, England) · 2026Article
- Uridine phosphorylase-1 supports metastasis by altering immune and extracellular matrix landscapes.EMBO reports · 2025Article
- Exosomes are specialized vehicles to induce fibronectin assembly.bioRxiv : the preprint server for biology · 2025Article
- SOAR elucidates biological insights and empowers drug discovery through spatial transcriptomics.Science advances · 2025Article
- Vemurafenib Induces Senescent Phenotype with Increased Adhesion in BRAF Mutant A375 but not in Wild Type BRAF SK-MEL-2 Melanoma Cells.Advanced pharmaceutical bulletin · 2025Article
- Mechanical forces in the tumor microenvironment: roles, pathways, and therapeutic approaches.Journal of translational medicine · 2025Review
- Single-cell analysis uncovers liver susceptibility to pancreatic cancer metastasis via myeloid cell characterization.Discover oncology · 2024Article
- SPP1+ macrophages in HR+ breast cancer are associated with tumor-infiltrating lymphocytes.NPJ breast cancer · 2024Article
- The importance of 3D fibre architecture in cancer and implications for biomaterial model design.Nature reviews. Cancer · 2024Review
- Imaging at the nexus: how state of the art imaging techniques can enhance our understanding of cancer and fibrosis.Journal of translational medicine · 2024Review
- Differential modulation of cellular phenotype and drug sensitivity by extracellular matrix proteins in primary and metastatic pancreatic cancer cells.Molecular biology of the cell · 2023Article
- Integrated analysis of single-cell and bulk RNA-sequencing reveals the poor prognostic value of ABCA1 in gastric adenocarcinoma.Discover oncology · 2023Article
- Cerebrospinal fluid exosomal protein alterations via proteomic analysis of NSCLC with leptomeningeal carcinomatosis.Journal of neuro-oncology · 2023Article
- Up-regulated SPP1 increases the risk from IPF to lung cancer via activating the pro-tumor macrophages.Computational and structural biotechnology journal · 2023Article
- Integrin subunit alpha V is a potent prognostic biomarker associated with immune infiltration in lower-grade glioma.Frontiers in neurology · 2022Article
- Longitudinal proteomic analysis of severe COVID-19 reveals survival-associated signatures, tissue-specific cell death, and cell-cell interactions.Cell reports. Medicine · 2021Article
- Fibronectin as a multiregulatory molecule crucial in tumor matrisome: from structural and functional features to clinical practice in oncology.Journal of experimental & clinical cancer research : CR · 2021Review
- Transcriptomic Profiling ofFrontiers in oncology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The seeding of tumor cells is a critical step in the process of metastasis, but whether and how the microenvironment of target organs affects metastatic seeding remain largely unknown. Based on cell and mouse models, we found that the metastatic seeding and outgrowth of tumor cells were significantly enhanced in fibrotic lungs. The conditioned medium from both fibrotic lungs and the fibrotic lung-derived fibroblasts (CM-FLF) had a strong activity to chemoattract tumor cells and to inhibit the apoptosis of tumor cells. Subsequent investigations revealed that the levels of fibronectin 1 (FN1) and secreted phosphoprotein 1 (SPP1) were significantly increased in fibrotic lungs. Silencing of FN1 in the fibrotic lung-derived fibroblasts dramatically decreased the chemoattracting activity of CM-FLF, while silencing of FN1 or SPP1 in fibroblasts attenuated the anti-apoptosis activity of CM-FLF. Moreover, the CM-FLF-induced apoptosis resistance or chemotaxis of tumor cells was attenuated when ITGAV, the common receptor of FN1 and SPP1, was silenced by RNA interference or blocked by GRGDS treatment in tumor cells. Consistently, ITGAV silencing or GRGDS treatment significantly inhibited the seeding and outgrowth of tumor cells in fibrotic lungs in vivo. Collectively, we suggest that fibrotic microenvironment may enhance the metastatic seeding of tumor cells in the lung by chemoattracting tumor cells and inhibiting their apoptosis via activating the FN1/SPP1-ITGAV signaling. These findings give a novel insight into the regulatory mechanisms of cancer metastasis and provide a potential target for anti-metastasis therapy.
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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.