ArticleNeoplasia (New York, N.Y.)2010
Metastasis in melanoma xenografts is associated with tumor microvascular density rather than extent of hypoxia.
Article in Neoplasia (New York, N.Y.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 38 citations in OpenAlex.
- Metastasis is impaired by endothelial-specific Dll4 loss-of-function through inhibition of epithelial-to-mesenchymal transition and reduction of cancer stem cells and circulating tumor cells.Clinical & experimental metastasis · 2019Article
- Intratumor Heterogeneity in Interstitial Fluid Pressure in Cervical and Pancreatic Carcinoma Xenografts.Translational oncology · 2019Article
- Metastatic pathway and the microvascular and physicochemical microenvironments of human melanoma xenografts.Journal of translational medicine · 2017Article
- Comparison of region-of-interest-averaged and pixel-averaged analysis of DCE-MRI data based on simulations and pre-clinical experiments.Physics in medicine and biology · 2017Article
- The Effect of Sunitinib Treatment in Human Melanoma Xenografts: Associations with Angiogenic Profiles.Translational oncology · 2017Article
- Properdistatin inhibits angiogenesis and improves vascular function in human melanoma xenografts with low thrombospondin-1 expression.Oncotarget · 2016Article
- Intracranial Tumor Cell Migration and the Development of Multiple Brain Metastases in Malignant Melanoma.Translational oncology · 2016Article
- Intertumor heterogeneity in vascularity and invasiveness of artificial melanoma brain metastases.Journal of experimental & clinical cancer research : CR · 2015Article
- Identification of Metastasis-Associated Metabolic Profiles of Tumors by (1)H-HR-MAS-MRS.Neoplasia (New York, N.Y.) · 2015Article
- Hematopoietic stem cell-derived cancer-associated fibroblasts are novel contributors to the pro-tumorigenic microenvironment.Neoplasia (New York, N.Y.) · 2015Article
- Tumor interstitial fluid pressure-a link between tumor hypoxia, microvascular density, and lymph node metastasis.Neoplasia (New York, N.Y.) · 2014Article
- Isolated limb infusion as a model to test new agents to treat metastatic melanoma.Journal of surgical oncology · 2014Review
- Overcoming intratumor heterogeneity of polygenic cancer drug resistance with improved biomarker integration.Neoplasia (New York, N.Y.) · 2012Article
- Bevacizumab-induced alterations in vascular permeability and drug delivery: a novel approach to augment regional chemotherapy for in-transit melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2012Article
- Objective assessment of blood and lymphatic vessel invasion and association with macrophage infiltration in cutaneous melanoma.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2012Article
- High interstitial fluid pressure is associated with tumor-line specific vascular abnormalities in human melanoma xenografts.PloS one · 2012Article
- The interconnectedness of cancer cell signaling.Neoplasia (New York, N.Y.) · 2011Article
- Minimally invasive intra-arterial regional therapy for metastatic melanoma: isolated limb infusion and percutaneous hepatic perfusion.Expert opinion on drug metabolism & toxicology · 2011Review
- Antiangiogenic therapy, hypoxia, and metastasis: risky liaisons, or not?Nature reviews. Clinical oncology · 2011Review
- Dinosaurs and ancient civilizations: reflections on the treatment of cancer.Neoplasia (New York, N.Y.) · 2010Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of metastases has been shown to be associated with the microvascular density of the primary tumor in some clinical studies and with the extent of hypoxia in others. The aim of this study was to investigate the validity of these apparently inconsistent observations and to reveal possible links between them. Xenografted tumors of nine melanoma cell lines established from patients with diseases differing in aggressiveness were studied. The aggressiveness of the cell lines was assessed by measuring their lung colonization potential, invasiveness, angiogenic potential, and tumorigenicity. Spontaneous metastasis was assessed in untreated mice and mice treated with neutralizing antibody against vascular endothelial growth factor A (VEGF-A) or interleukin 8 (IL-8). Microvascular density was scored in histologic preparations. Hypoxic fractions were measured by using a radiobiologic assay and a pimonidazole-based immunohistochemical assay. The aggressiveness of the melanoma lines reflected the aggressiveness of the donor patients' tumors. The metastatic propensity was associated with the microvascular density but not with the hypoxic fraction. Anti-VEGF-A and anti-IL-8 treatments resulted in decreased microvascular density and reduced incidence of metastases in all lines. Large hypoxic fractions were not a secondary effect of high cellular aggressiveness, whereas the microvascular density was associated with the cellular aggressiveness. The metastatic propensity was governed by the angiogenic potential of the tumor cells. The differences in microvascular density among the lines were most likely a consequence of differences in the constitutive angiogenic potential rather than differences in hypoxia-induced angiogenesis. VEGF-A and IL-8 may be important therapeutic targets for melanoma.
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