ArticleThe American journal of pathology2008
Tumor recovery by angiogenic switch from sprouting to intussusceptive angiogenesis after treatment with PTK787/ZK222584 or ionizing radiation.
Article in The American journal of pathology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 134 citations in OpenAlex.
- Linking preclinical models with functional imaging and artificial intelligence to decode tumor angiogenesis.Pharmacological reports : PR · 2026Review
- The cellular dance that splits vessels.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Intussusceptive angiogenesis-on-a-chip: Evidence for transluminal vascular bridging by endothelial delamination.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Understanding Neovascularization in Glioblastoma: Insights from the Current Literature.International journal of molecular sciences · 2025Review
- Radiotherapy elicits immunogenic cell death and metabolic shifts in the tumor microenvironment: implications for immunotherapy.International journal of medical sciences · 2025Review
- The role of vasculature and angiogenesis in respiratory diseases.Angiogenesis · 2024Review
- Feedback loop between hypoxia and energy metabolic reprogramming aggravates the radioresistance of cancer cells.Experimental hematology & oncology · 2024Review
- VEGF signaling: Role in angiogenesis and beyond.Biochimica et biophysica acta. Reviews on cancer · 2024Review
- Mechanisms of angiogenesis in tumour.Frontiers in oncology · 2024Review
- Article
- Amygdalin-folic acid-nanoparticles inhibit the proliferation of breast cancer and enhance the effect of radiotherapy through the modulation of tumor-promoting factors/ immunosuppressive modulators in vitro.BMC complementary medicine and therapies · 2023Article
- Deciphering endothelial heterogeneity in health and disease at single-cell resolution: progress and perspectives.Cardiovascular research · 2023Article
- The emerging potential of quantitative MRI biomarkers for the early prediction of brain metastasis response after stereotactic radiosurgery: a scoping review.Quantitative imaging in medicine and surgery · 2023Article
- SARS-CoV-2 and Endothelial Cells: Vascular Changes, Intussusceptive Microvascular Growth and Novel Therapeutic Windows.Biomedicines · 2022Review
- Comparison of the Behavior of Perivascular Cells (Pericytes and CD34+ Stromal Cell/Telocytes) in Sprouting and Intussusceptive Angiogenesis.International journal of molecular sciences · 2022Review
- Issues of origin, morphology and clinical significance of tumor microvessels in gastric cancer.World journal of gastroenterology · 2021Review
- Propensity for Early Metastatic Spread in Breast Cancer: Role of Tumor Vascularization Features and Tumor Immune Infiltrate.Cancers · 2021Review
- Intussusceptive Angiogenesis in Human Metastatic Malignant Melanoma.The American journal of pathology · 2021Article
- Article
- Interfering with Tumor Hypoxia for Radiotherapy Optimization.Journal of experimental & clinical cancer research : CR · 2021Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inhibitors of angiogenesis and radiation induce compensatory changes in the tumor vasculature both during and after treatment cessation. To assess the responses to irradiation and vascular endothelial growth factor-receptor tyrosine kinase inhibition (by the vascular endothelial growth factor tyrosine kinase inhibitor PTK787/ZK222854), mammary carcinoma allografts were investigated by vascular casting; electron, light, and confocal microscopy; and immunoblotting. Irradiation and anti-angiogenic therapy had similar effects on the tumor vasculature. Both treatments reduced tumor vascularization, particularly in the tumor medulla. After cessation of therapy, the tumor vasculature expanded predominantly by intussusception with a plexus composed of enlarged sinusoidal-like vessels containing multiple transluminal tissue pillars. Tumor revascularization originated from preserved alpha-smooth muscle actin-positive vessels in the tumor cortex. Quantification revealed that recovery was characterized by an angiogenic switch from sprouting to intussusception. Up-regulated alpha-smooth muscle actin-expression during recovery reflected the recruitment of alpha-smooth muscle actin-positive cells for intussusception as part of the angio-adaptive mechanism. Tumor recovery was associated with a dramatic decrease (by 30% to 40%) in the intratumoral microvascular density, probably as a result of intussusceptive pruning and, surprisingly, with only a minimal reduction of the total microvascular (exchange) area. Therefore, the vascular supply to the tumor was not severely compromised, as demonstrated by hypoxia-inducible factor-1alpha expression. Both irradiation and anti-angiogenic therapy cause a switch from sprouting to intussusceptive angiogenesis, representing an escape mechanism and accounting for the development of resistance, as well as rapid recovery, after cessation of therapy.
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