ArticleMolecular cancer2013
Podoplanin expression in cancer-associated fibroblasts enhances tumor progression of invasive ductal carcinoma of the pancreas.
Article in Molecular cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 1 of them a synthesis that pooled it.
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Who cites it
105 citing papers in PubMed, 1 synthesis or guideline pooled it, 155 citations in OpenAlex.
- Podoplanin Expression and the Risk of Malignant Transformation of Oral Pre-Malignant Disease: A Systematic Review and Meta-Analysis.Head & neck · 2025Pooled it
- Immune-driven stromal inflammation in pancreatic cancer within a microfluidic platform.Biofabrication · 2026Article
- From Physiology to Clinical Practice in Pancreatic Cancer-Related Thromboembolism-A Review.Cancers · 2026Review
- Prognostic value of multiparameter [European journal of nuclear medicine and molecular imaging · 2026Article
- Vascular Toxicities of Cancer Therapies: 2025 Update.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Prognostic significance of fibroblast senescence and senescence-associated secretory phenotype factor expression in the tumor microenvironment of pancreatic ductal adenocarcinoma.Oncology reports · 2026Article
- Near Infrared Photoimmunotherapy for Lung Cancer: Recent Development and Perspective.ImmunoTargets and therapy · 2026Review
- The LVI Component Hypothesis: the lymphatic-to-vascular invasion ratio as an enrichment biomarker for therapy with PD-L1×VEGF-A bispecific antibodies.Frontiers in immunology · 2026Article
- Over-Expression of TNFRSF12A Promotes Immune Suppression and Facilitates Angiogenesis in Triple-Negative Breast Cancer.Biology · 2025Article
- Healthy BRCA1/2 mutation carriers exhibit a pre-CAF signature and altered epithelial marker expression in breast tissue.Scientific reports · 2025Article
- Review
- Proteomic profiling identifies a stromal TGF-β1/podoplanin axis as a driver of colorectal cancer progression.Journal of experimental & clinical cancer research : CR · 2025Article
- Review
- Patient derived cancer-associated fibroblasts from non-small cell lung cancer undergo phenotypic drift in culture.BJC reports · 2025Article
- The Tumour Glyco-Code: Sialylation as a Mediator of Stromal Cell Immunosuppression in the Tumour Microenvironment.European journal of immunology · 2025Review
- Overcoming cancer treatment resistance: Unraveling the role of cancer-associated fibroblasts.Journal of the National Cancer Center · 2025Review
- Stromal Cell Subsets Show Model-Dependent Changes in Experimental Colitis and Affect Epithelial Tissue Repair and Immune Cell Activation.Inflammatory bowel diseases · 2025Article
- Chemokine (C-C Motif) Ligand 2/CCR2/Extracellular Signal-Regulated Kinase Signal Induced through Cancer Cell-Macrophage Interaction Contributes to Hepatocellular Carcinoma Progression.The American journal of pathology · 2025Article
- Cancer-associated fibroblasts as therapeutic targets for cancer: advances, challenges, and future prospects.Journal of biomedical science · 2025Review
- Article
45 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInteractions between cancer cells and surrounding cancer-associated fibroblasts (CAFs) play an important role in cancer progression. Invasive ductal carcinoma (IDC) of the pancreas is characterized by abundant fibrous connective tissue called desmoplasia. Podoplanin (PDPN) is a lymphatic vessel marker (D2-40), and expression of PDPN by stromal CAFs has been reported to be a prognostic indicator in various types of cancer.
methodsExpression of PDPN in pancreatic IDCs was assessed by immunohistochemical examination in 105 patients who underwent pancreatic resection. Primary CAFs were established from pancreatic cancer tissue obtained by surgery. Quantitative reverse transcription-polymerase chain reaction and flow cytometric analysis were performed to investigate PDPN expression in CAFs. We sorted CAFs according to PDPN expression, and analyzed the functional differences between PDPN+ CAFs and PDPN- CAFs using indirect co-culture with pancreatic cancer cell lines. We also investigated the culture conditions to regulate PDPN expression in CAFs.
resultsPDPN expression in stromal fibroblasts was associated with lymphatic vessel invasion (P = 0.0461), vascular invasion (P = 0.0101), tumor size ≥ 3 cm (P = 0.0038), histological grade (P = 0.0344), Union for International Cancer Control classification T stage (P = 0.029), and shorter survival time (P < 0.0001). Primary CAFs showed heterogeneous PDPN expression in vitro. Moreover, migration and invasion of pancreatic cancer cell lines (PANC-1 and SUIT-2) were associated with PDPN expression in CAFs (P < 0.01) and expression of CD10, matrix metalloproteinase (MMP) 2, and MMP3. In cultured CAFs, PDPN positivity changed over time under several conditions including co-culture with cancer cells, different culture media, and addition of growth factor.
conclusionsPDPN-expressing CAFs enhance the progression of pancreatic IDC, and a high ratio of PDPN-expressing CAFs is an independent predictor of poor outcome. Understanding the regulation of the tumor microenvironment is an important step towards developing new therapeutic strategies.
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