ArticleClinical cancer research : an official journal of the American Association for Cancer Research2011
Stromal LRP1 in lung adenocarcinoma predicts clinical outcome.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- Functional impact of multi-omic interactions in lung cancer.Frontiers in genetics · 2024Article
- Molecular typing and mutational characterization of rectal neuroendocrine neoplasms.Cancer medicine · 2023Article
- Multi-faceted role of LRP1 in the immune system.Frontiers in immunology · 2023Review
- MIF promotes cell invasion by the LRP1-uPAR interaction in pancreatic cancer cells.Frontiers in oncology · 2022Article
- Identification of personalized neoantigen-based vaccines and immune subtype characteristic analysis of glioblastoma based on abnormal alternative splicing.American journal of cancer research · 2022Article
- Identification of a novel metabolism-related gene signature associated with the survival of bladder cancer.BMC cancer · 2021Article
- Connecting Cholesterol Efflux Factors to Lung Cancer Biology and Therapeutics.International journal of molecular sciences · 2021Review
- Single-Cell Transcriptome Analysis Identifies Ligand-Receptor Pairs Associated With BCP-ALL Prognosis.Frontiers in oncology · 2021Article
- Proteomic Profiling of Retinoblastoma-Derived Exosomes Reveals Potential Biomarkers of Vitreous Seeding.Cancers · 2020Article
- Actionable Potentials of Less Frequently Mutated Genes in Colorectal Cancer and Their Roles in Precision Medicine.Biomolecules · 2020Review
- CD200 and CD200R1 are differentially expressed and have differential prognostic roles in non-small cell lung cancer.Oncoimmunology · 2020Article
- LRP1 expression in colon cancer predicts clinical outcome.Oncotarget · 2018Article
- TheBalkan journal of medical genetics : BJMG · 2017Article
- LRP-1 Pathway Targeted Inhibition of Vascular Abnormalities in the Retina of Diabetic Mice.Current eye research · 2017Article
- Verification and characterization of an alternative low density lipoprotein receptor-related protein 1 splice variant.PloS one · 2017Article
- Article
- Roles of low-density lipoprotein receptor-related protein 1 in tumors.Chinese journal of cancer · 2016Review
- A Role for Low Density Lipoprotein Receptor-Related Protein 1 in the Cellular Uptake of Tissue Plasminogen Activator in the Lungs.Pharmaceutical research · 2016Article
- Identification of a multi-cancer gene expression biomarker for cancer clinical outcomes using a network-based algorithm.Scientific reports · 2015Article
- The Matricellular Receptor LRP1 Forms an Interface for Signaling and Endocytosis in Modulation of the Extracellular Tumor Environment.Frontiers in pharmacology · 2015Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
purposeLRP1 (low-density lipoprotein receptor-related protein 1) is a broadly expressed receptor that binds multiple extracellular ligands and participates in protein clearance. It is expressed in numerous cancers, but its role in lung cancer has not been characterized. Here, we investigate the relationship between LRP1 and lung cancer. EXPERIMENTAL
designLRP1 mRNA levels were determined in lung tumors from several large, multicenter studies. LRP1 protein localization was determined by immunohistochemical analysis of lung tumor microarrays. Normal fibroblasts, fibroblasts treated with the LRP1 inhibitor RAP (receptor-associated protein), and Lrp1 null fibroblasts were cocultured with 3 independent lung cancer cell lines to investigate the role of LRP1 on tumor cell proliferation.
resultsLRP1 mRNA levels are significantly decreased in lung tumors relative to nontumorous lung tissue. Lower expression of LRP1 in lung adenocarcinomas correlates with less favorable clinical outcome in a cohort of 439 patients. Immunohistochemical analysis shows that LRP1 is primarily expressed in stromal cells in 94/111 lung cancers, with very little protein found in cancer cells. A growth-suppressive function of mouse embryonic fibroblast (MEF) cells was observed in 3 lung cancer cell lines tested (H460, H2347, and HCC4006 cells); growth suppression was blocked by the LRP1 inhibitor RAP. Lrp1 deletion in fibroblasts reduced the ability of MEF cells to suppress tumor cell mitosis. In a validation set of adenocarcinomas, we confirmed a significant, positive correlation between both LRP1 mRNA and protein levels and favorable clinical outcomes.
conclusionsLRP1 expression is associated with improved lung cancer outcomes. Mechanistically, stromal LRP1 may non-cell autonomously suppress lung tumor cell proliferation.
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