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The roles of platelet-derived growth factors and their receptors in brain radiation necrosis.

Miyata T, Toho T, Nonoguchi N, Furuse M, Kuwabara H, Yoritsune E, Kawabata S, Kuroiwa T, Miyatake S - Radiat Oncol (2014)

Bottom Line: All PDGFs were expressed in macrophages, microglia, and endothelial cells in the boundary of the core of RN, namely, the perinecrotic area (PN), as well as in undamaged brain tissue (UB).PDGF-C, D and PDGFR-α were also expressed in reactive astrocytes in PN.PDGFs and PDGFR-α were scarcely detected in UB, but PDGFR-β was specifically expressed in endothelial cells not only in PN but also in UB.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurosurgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki City, Osaka 569-8686, Japan. neu070@poh.osaka-med.ac.jp.

ABSTRACT

Background: Brain radiation necrosis (RN) occurring after radiotherapy is a serious complication. We and others have performed several treatments for RN, using anticoagulants, corticosteroids, surgical resection and bevacizumab. However, the mechanisms underlying RN have not yet been completely elucidated. For more than a decade, platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) have been extensively studied in many biological processes. These proteins influence a wide range of biological responses and participate in many normal and pathological conditions. In this study, we demonstrated that PDGF isoforms (PDGF-A, B, C, and D) and PDGFRs (PDGFR-α and β) are involved in the pathogenesis of human brain RN. We speculated on their roles, with a focus on their potential involvement in angiogenesis and inflammation in RN.

Methods: Seven surgical specimens of RN, obtained from 2006 to 2013 at our department, were subjected to histopathological analyses and stained with hematoxylin and eosin. We qualitatively analyzed the protein expression of each isoform of PDGF by immunohistochemistry. We also examined their expression with double immunofluorescence.

Results: All PDGFs were expressed in macrophages, microglia, and endothelial cells in the boundary of the core of RN, namely, the perinecrotic area (PN), as well as in undamaged brain tissue (UB). PDGF-C, D and PDGFR-α were also expressed in reactive astrocytes in PN. PDGFs and PDGFR-α were scarcely detected in UB, but PDGFR-β was specifically expressed in endothelial cells not only in PN but also in UB.

Conclusions: PDGFs/PDGFRs play critical roles in angiogenesis and possibly in inflammation, and they contribute to the pathogenesis of RN, irrespective of the original tumor pathology and applied radiation modality. Treatments for the inhibition of PDGF-C, PDGF-D, and PDGFR-α may provide new approaches for the treatment of RN induced by common radiation therapies.

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Related in: MedlinePlus

Double immunofluorescence staining. Double immunofluorescence staining from case 1 revealed that PDGFR-α and β were strongly expressed in CD31-positive cells in PN (D and I). PDGFR-α positive cells were merged with many cells positive for CD68 (A), GFAP (B), hGLUT5 (C), and CD45 (E). PDGFR-β-positive cells merged specifically with endothelial cells (F, G, H, I and J, *). Endothelial cells (*) were nonspecifically stained with secondary fluorescence antibody. The scale bar represents 50 μm.
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Figure 5: Double immunofluorescence staining. Double immunofluorescence staining from case 1 revealed that PDGFR-α and β were strongly expressed in CD31-positive cells in PN (D and I). PDGFR-α positive cells were merged with many cells positive for CD68 (A), GFAP (B), hGLUT5 (C), and CD45 (E). PDGFR-β-positive cells merged specifically with endothelial cells (F, G, H, I and J, *). Endothelial cells (*) were nonspecifically stained with secondary fluorescence antibody. The scale bar represents 50 μm.

Mentions: Double immunofluorescence revealed that PDGFR-α and β were strongly expressed in CD31-positive cells (Figure 5D, I). PDGFR-β-positive cells were merged specifically with endothelial cells (Figure 5F, G, H, I and J, *), but PDGFR-α-positive cells were merged with cells positive for CD68 (Figure 5A), GFAP (Figure 5B), hGLUT5 (Figure 5C), and CD45 (Figure 5E) in PN.


The roles of platelet-derived growth factors and their receptors in brain radiation necrosis.

Miyata T, Toho T, Nonoguchi N, Furuse M, Kuwabara H, Yoritsune E, Kawabata S, Kuroiwa T, Miyatake S - Radiat Oncol (2014)

Double immunofluorescence staining. Double immunofluorescence staining from case 1 revealed that PDGFR-α and β were strongly expressed in CD31-positive cells in PN (D and I). PDGFR-α positive cells were merged with many cells positive for CD68 (A), GFAP (B), hGLUT5 (C), and CD45 (E). PDGFR-β-positive cells merged specifically with endothelial cells (F, G, H, I and J, *). Endothelial cells (*) were nonspecifically stained with secondary fluorescence antibody. The scale bar represents 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3927833&req=5

Figure 5: Double immunofluorescence staining. Double immunofluorescence staining from case 1 revealed that PDGFR-α and β were strongly expressed in CD31-positive cells in PN (D and I). PDGFR-α positive cells were merged with many cells positive for CD68 (A), GFAP (B), hGLUT5 (C), and CD45 (E). PDGFR-β-positive cells merged specifically with endothelial cells (F, G, H, I and J, *). Endothelial cells (*) were nonspecifically stained with secondary fluorescence antibody. The scale bar represents 50 μm.
Mentions: Double immunofluorescence revealed that PDGFR-α and β were strongly expressed in CD31-positive cells (Figure 5D, I). PDGFR-β-positive cells were merged specifically with endothelial cells (Figure 5F, G, H, I and J, *), but PDGFR-α-positive cells were merged with cells positive for CD68 (Figure 5A), GFAP (Figure 5B), hGLUT5 (Figure 5C), and CD45 (Figure 5E) in PN.

Bottom Line: All PDGFs were expressed in macrophages, microglia, and endothelial cells in the boundary of the core of RN, namely, the perinecrotic area (PN), as well as in undamaged brain tissue (UB).PDGF-C, D and PDGFR-α were also expressed in reactive astrocytes in PN.PDGFs and PDGFR-α were scarcely detected in UB, but PDGFR-β was specifically expressed in endothelial cells not only in PN but also in UB.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurosurgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki City, Osaka 569-8686, Japan. neu070@poh.osaka-med.ac.jp.

ABSTRACT

Background: Brain radiation necrosis (RN) occurring after radiotherapy is a serious complication. We and others have performed several treatments for RN, using anticoagulants, corticosteroids, surgical resection and bevacizumab. However, the mechanisms underlying RN have not yet been completely elucidated. For more than a decade, platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) have been extensively studied in many biological processes. These proteins influence a wide range of biological responses and participate in many normal and pathological conditions. In this study, we demonstrated that PDGF isoforms (PDGF-A, B, C, and D) and PDGFRs (PDGFR-α and β) are involved in the pathogenesis of human brain RN. We speculated on their roles, with a focus on their potential involvement in angiogenesis and inflammation in RN.

Methods: Seven surgical specimens of RN, obtained from 2006 to 2013 at our department, were subjected to histopathological analyses and stained with hematoxylin and eosin. We qualitatively analyzed the protein expression of each isoform of PDGF by immunohistochemistry. We also examined their expression with double immunofluorescence.

Results: All PDGFs were expressed in macrophages, microglia, and endothelial cells in the boundary of the core of RN, namely, the perinecrotic area (PN), as well as in undamaged brain tissue (UB). PDGF-C, D and PDGFR-α were also expressed in reactive astrocytes in PN. PDGFs and PDGFR-α were scarcely detected in UB, but PDGFR-β was specifically expressed in endothelial cells not only in PN but also in UB.

Conclusions: PDGFs/PDGFRs play critical roles in angiogenesis and possibly in inflammation, and they contribute to the pathogenesis of RN, irrespective of the original tumor pathology and applied radiation modality. Treatments for the inhibition of PDGF-C, PDGF-D, and PDGFR-α may provide new approaches for the treatment of RN induced by common radiation therapies.

Show MeSH
Related in: MedlinePlus