ArticleOncotarget2017
Human CAFs promote lymphangiogenesis in ovarian cancer via the Hh-VEGF-C signaling axis.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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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.
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Who cites it
34 citing papers in PubMed, 42 citations in OpenAlex.
- MEOX1 Coordinates Autocrine-Paracrine Programs via SPHK1/S1P to Promote Lymph Node Metastasis in Ovarian Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Critical roles of Hedgehog signaling pathway in regulating the multidrug resistance of ovarian cancer.Journal of ovarian research · 2026Review
- Lymphatic Endothelial Cells and Organ-Associated Lymphangiogenesis in Tumor Microenvironment.Cells · 2025Review
- The Prognostic Value of the Hedgehog Signaling Pathway in Ovarian Cancer.International journal of molecular sciences · 2025Article
- Role of tumor microenvironment in ovarian cancer metastasis and clinical advancements.Journal of translational medicine · 2025Review
- Fruquintinib saddles tumor immune tolerance by curbing pro-tumoral immature myeloid cell populations.Frontiers in immunology · 2025Article
- Tumor-associated fibrosis: a unique mechanism promoting ovarian cancer metastasis and peritoneal dissemination.Cancer metastasis reviews · 2024Review
- Patient-Derived Primary Cancer-Associated Fibroblasts Mediate Resistance to Anti-Angiogenic Drug in Ovarian Cancers.Biomedicines · 2023Article
- Dual effects of radiotherapy on tumor microenvironment and its contribution towards the development of resistance to immunotherapy in gastrointestinal and thoracic cancers.Frontiers in cell and developmental biology · 2023Review
- Review
- Cancer-associated fibroblasts in nonsmall cell lung cancer: From molecular mechanisms to clinical implications.International journal of cancer · 2022Review
- Review
- Noncoding RNAs related to the hedgehog pathway in cancer: clinical implications and future perspectives.Molecular cancer · 2022Review
- Cancer Stem Cells in Ovarian Cancer-A Source of Tumor Success and a Challenging Target for Novel Therapies.International journal of molecular sciences · 2022Review
- [Progress in the Mechanism of Lymphangiogenesis and Lymphatic Metastasis of Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2021Review
- Microenvironmental modulation of the developing tumour: an immune-stromal dialogue.Molecular oncology · 2021Review
- Role of lymphatic endothelial cells in the tumor microenvironment-a narrative review of recent advances.Translational lung cancer research · 2021Review
- Metabolomics revealed the influence of breast cancer on lymphatic endothelial cell metabolism, metabolic crosstalk, and lymphangiogenic signaling in co-culture.Scientific reports · 2020Article
- Cancer-associated fibroblasts, matrix metalloproteinase-9 and lymphatic vessel density are associated with progression from adenocarcinomaOncology letters · 2020Article
- VEGFC negatively regulates the growth and aggressiveness of medulloblastoma cells.Communications biology · 2020Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
Cancer-associated fibroblasts (CAFs) play a pivotal role in the development and progression of many human cancers. Recent studies have shown that Hedgehog (Hh) signalling modulates the stromal microenvironment and prepares a suitable niche for tumour metastasis. However, the detailed molecular mechanisms underlying CAF-mediated lymphangiogenesis have not been fully elucidated. Therefore, our goal is to illustrate whether Hh ligands can activate Hh signalling in CAFs in a paracrine fashion and elucidate the effect of CAFs on lymphangiogenesis. We determined here that Sonic Hedgehog (SHH) secreted by ovarian cancer (OC) cells activated Hh signalling in CAFs and promoted the proliferation of CAFs. Moreover, we co-injected SHH-overexpressing OC cells and CAFs in a xenograft model and found that the CAFs accelerated tumourigenesis and lymphangiogenesis in OC. Mechanistically, we found that SHH secreted by the OC cells induced VEGF-C expression in CAFs. Inhibition of Hh signalling in CAFs decreased VEGF-C expression and diminished the positive role of CAFs in supporting tumourigenesis and lymphangiogenesis in a murine xenograft model. Our results demonstrate that CAFs constitute a supportive niche for cancer lymphangiogenesis via the Hh/VEGF-C signalling axis and provide evidence for the clinical application of Hh inhibitors in the treatment of OC.
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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.