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Vasculatures in tumors growing from preirradiated tissues: formed by vasculogenesis and resistant to radiation and antiangiogenic therapy
- Source :
- International journal of radiation oncology, biology, physics. 80(5)
- Publication Year :
- 2010
-
Abstract
- Purpose To investigate vasculatures and microenvironment in tumors growing from preirradiated tissues (pre-IR tumors) and study the vascular responses of pre-IR tumors to radiation and antiangiogenic therapy. Methods and Materials Transgenic adenocarcinoma of the mouse prostate C1 tumors were implanted into unirradiated or preirradiated tissues and examined for vascularity, hypoxia, and tumor-associated macrophage (TAM) infiltrates by immunohistochemistry. The origin of tumor endothelial cells was studied by green fluorescent protein–tagged bone marrow (GFP-BM) transplantation. The response of tumor endothelial cells to radiation and antiangiogenic agent was evaluated by apoptotic assay. Results The pre-IR tumors had obvious tumor bed effects (TBE), with slower growth rate, lower microvascular density (MVD), and more necrotic and hypoxic fraction compared with control tumors. The vessels were dilated, tightly adhered with pericytes, and incorporated with transplanted GFP-BM cells. In addition, hypoxic regions became aggregated with TAM. As pre-IR tumors developed, the TBE was overcome at the tumor edge where the MVD increased, TAM did not aggregate, and the GFP-BM cells did not incorporate into the vessels. The vessels at tumor edge were more sensitive to the following ionizing radiation and antiangiogenic agent than those in the central low MVD regions. Conclusions This study demonstrates that vasculatures in regions with TBE are mainly formed by vasculogenesis and resistant to radiation and antiangiogenic therapy. Tumor bed effects could be overcome at the edge of larger tumors, but where vasculatures are formed by angiogenesis and sensitive to both treatments. Vasculatures formed by vasculogenesis should be the crucial target for the treatment of recurrent tumors after radiotherapy.
- Subjects :
- Male
Cancer Research
Pathology
Radiation-Sensitizing Agents
Indoles
Neoplasms, Radiation-Induced
Angiogenesis
medicine.medical_treatment
Angiogenesis Inhibitors
Radiation Tolerance
Neovascularization
Mice
Sunitinib
Tumor Microenvironment
Coloring Agents
Bone Marrow Transplantation
Cell Aggregation
Radiation
Neovascularization, Pathologic
Cell Hypoxia
Tumor Burden
medicine.anatomical_structure
Oncology
Nitroimidazoles
Immunohistochemistry
Adenocarcinoma
medicine.symptom
medicine.medical_specialty
Green Fluorescent Proteins
Radiation Dosage
Vasculogenesis
Cell Line, Tumor
medicine
Animals
Radiology, Nuclear Medicine and imaging
Pyrroles
Salvage Therapy
business.industry
Macrophages
Endothelial Cells
Prostatic Neoplasms
medicine.disease
Xenograft Model Antitumor Assays
Radiation therapy
Transplantation
Mice, Inbred C57BL
Drug Resistance, Neoplasm
Bone marrow
Neoplasm Recurrence, Local
business
Subjects
Details
- ISSN :
- 1879355X
- Volume :
- 80
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- International journal of radiation oncology, biology, physics
- Accession number :
- edsair.doi.dedup.....c9f8e0f915150bd3b3f7d2c379643b27