ArticleNeoplasia (New York, N.Y.)2014
Tumor interstitial fluid pressure-a link between tumor hypoxia, microvascular density, and lymph node metastasis.
Article in Neoplasia (New York, N.Y.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 136 citations in OpenAlex.
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- Recent advances in interstitial fluid dynamics for diagnostic, targeted drug delivery and precision medicine applications.Drug delivery and translational research · 2026Review
- Reimagining Nodal Staging in Colorectal Cancer: Toward a Novel Non-Invasive Imaging Approach.Cancers · 2026Review
- The role of ECM mechanics in cancer mechanotransduction through unraveling the molecular machinery of integrins, FAK, and YAP signaling.Cellular & molecular biology letters · 2026Review
- Mechanical regulation of microenvironment remodeling in brain tumors: from mechanism to therapy.Journal of neuroinflammation · 2026Review
- The Potential Role of Tumor Microorganisms in Remodeling Tumor Biomechanical Signals and Application Strategies in Tumor Therapy.Microorganisms · 2026Review
- Effect of Lymphatic Invasion on Survival and Recurrence After Liver Transplantation in Patients with Hepatocellular Carcinoma and Its Prognostic Significance.Diagnostics (Basel, Switzerland) · 2026Article
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- RSK4 promotes the metastasis of clear cell renal cell carcinoma by activating RUNX1-mediated angiogenesis.Cancer biology & therapy · 2025Article
- Lymphatic collection and cell isolation from mouse models for multiomic profiling.Nature protocols · 2025Review
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- Regulation of VEGFR3 signaling in lymphatic endothelial cells.Frontiers in cell and developmental biology · 2025Review
- Mechanical signatures in cancer metastasis.npj biological physics and mechanics · 2025Review
- Non-small cell lung cancer organoids: Advances and challenges in current applications.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- Article
- Hypoxia-Inducible Factor 1-Alpha (HIF-1α) and Cancer: Mechanisms of Tumor Hypoxia and Therapeutic Targeting.Cureus · 2024Review
- Pressure-enhanced sensing of tissue oxygenation via endogenous porphyrin: Implications for dynamic visualization of cancer in surgery.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Development of injectable colloidal solution forming anBiomaterials science · 2024Article
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- Vascular phenotyping of the invasive front in breast cancer using a 3D angiogenesis atlas.Microvascular research · 2023Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High microvascular density (MVD) in the primary tumor has been shown to be associated with increased incidence of lymph node metastases and poor clinical outcome. Other investigations have revealed that a large fraction of hypoxic tissue in the primary tumor is associated with metastatic disease and impaired survival. These data are apparently incompatible because tumor hypoxia is primarily a consequence of poor oxygen supply caused by an inadequate vasculature with increased intervessel distances. Here, we provide an explanation of these observations. Human melanoma xenografts were used as preclinical cancer models. Tumors that metastasized to lymph nodes showed higher interstitial fluid pressure (IFP) than those that did not metastasize, and compared with tumors with low IFP, tumors with high IFP showed large hypoxic fractions centrally, high MVD in the periphery, high peritumoral density of lymphatics, and elevated expression of vascular endothelial growth factor A (VEGF-A) and VEGF-C. Significant correlations were found between peripheral MVD and central hypoxia, and lymph node metastasis was associated with high values of both parameters. These findings suggest that the outcome of cancer may be associated with both high MVD and extensive hypoxia in the primary tumor. We propose that proangiogenic factors are upregulated in the tumor center and that the outward interstitial fluid flow caused by the elevated IFP transports these factors to the tumor surface where they evoke hemangiogenesis and lymphangiogenesis, and consequently, that the IFP serves as a link between tumor hypoxia, peripheral tumor hemangiogenesis, peritumoral lymphangiogenesis, and lymph node metastasis.
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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.