ArticleThe Journal of clinical investigation2018
Cancer-associated fibroblasts regulate endothelial adhesion protein LPP to promote ovarian cancer chemoresistance.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
88 citing papers in PubMed, 1 synthesis or guideline pooled it, 130 citations in OpenAlex.
- Genetic determinants of skin ageing: a systematic review and meta-analysis of genome-wide association studies and candidate genes.Journal of physiological anthropology · 2025Pooled it
- S100A4 characterize antigen-presenting cancer-associated fibroblasts and predicts surgical outcomes in relapsed ovarian cancer.Therapeutic advances in medical oncology · 2026Article
- Loss of MFAP5 and Its Effect on Skin Homeostasis and Wound Healing.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Role of the tumor microenvironment in chemotherapy resistance in ovarian cancer and targeted therapy.Journal of ovarian research · 2025Review
- Cancer-associated fibroblasts are associated with neo-adjuvant treatment response in oesophageal adenocarcinoma.British journal of cancer · 2025Article
- Chemoresistance Evolution in Ovarian Cancer Delineated by Single-Cell RNA Sequencing.International journal of molecular sciences · 2025Article
- Role of tumor microenvironment in ovarian cancer metastasis and clinical advancements.Journal of translational medicine · 2025Review
- Deciphering the stromal molecular landscape: the correlation between p16 and α-SMA in epithelial ovarian cancer.Journal of cancer research and clinical oncology · 2025Article
- Crosstalk between stromal, immune, and ovarian cancer cells in lipid-rich tumor microenvironment exhibits proliferative features.Frontiers in immunology · 2025Review
- Cancer-associated fibroblasts in ovarian cancer: research progress.Frontiers in oncology · 2025Review
- Competing endogenous RNAs network dysregulation in oral cancer: a multifaceted perspective on crosstalk and competition.Cancer cell international · 2024Review
- Integrating histopathology and transcriptomics for spatial tumor microenvironment profiling in a melanoma case study.NPJ precision oncology · 2024Article
- Multicompartmentalized Microvascularized Tumor-on-a-Chip to Study Tumor-Stroma Interactions and Drug Resistance in Ovarian Cancer.Cellular and molecular bioengineering · 2024Article
- Vascularized platforms for investigating cell communication via extracellular vesicles.Biomicrofluidics · 2024Review
- CAFs vs. TECs: when blood feuds fuel cancer progression, dissemination and therapeutic resistance.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Exploring the Potential of Natural Killer Cell-Based Immunotherapy in Targeting High-Grade Serous Ovarian Carcinomas.Vaccines · 2024Review
- miR-200-mediated inactivation of cancer-associated fibroblasts via targeting of NRP2-VEGFR signaling attenuates lung cancer invasion and metastasis.Molecular therapy. Nucleic acids · 2024Article
- Review
- Proteomics and Bioinformatics Investigations Link Overexpression of FGF8 and Associated Hub Genes to the Progression of Ovarian Cancer and Poor Prognosis.Biochemistry research international · 2024Article
- Cancer-associated fibroblast cell surface markers as potential biomarkers or therapeutic targets in lung cancer.Cancer drug resistance (Alhambra, Calif.) · 2024Review
28 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
12 authors at 4 institutions in 2 countries.
Funding
Abstract
The molecular mechanism by which cancer-associated fibroblasts (CAFs) confer chemoresistance in ovarian cancer is poorly understood. The purpose of the present study was to evaluate the roles of CAFs in modulating tumor vasculature, chemoresistance, and disease progression. Here, we found that CAFs upregulated the lipoma-preferred partner (LPP) gene in microvascular endothelial cells (MECs) and that LPP expression levels in intratumoral MECs correlated with survival and chemoresistance in patients with ovarian cancer. Mechanistically, LPP increased focal adhesion and stress fiber formation to promote endothelial cell motility and permeability. siRNA-mediated LPP silencing in ovarian tumor-bearing mice improved paclitaxel delivery to cancer cells by decreasing intratumoral microvessel leakiness. Further studies showed that CAFs regulate endothelial LPP via a calcium-dependent signaling pathway involving microfibrillar-associated protein 5 (MFAP5), focal adhesion kinase (FAK), ERK, and LPP. Thus, our findings suggest that targeting endothelial LPP enhances the efficacy of chemotherapy in ovarian cancer. Our data highlight the importance of CAF-endothelial cell crosstalk signaling in cancer chemoresistance and demonstrate the improved efficacy of using LPP-targeting siRNA in combination with cytotoxic drugs.
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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.