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Expression of integrin alphavbeta3 in gliomas correlates with tumor grade and is not restricted to tumor vasculature.

Schnell O, Krebs B, Wagner E, Romagna A, Beer AJ, Grau SJ, Thon N, Goetz C, Kretzschmar HA, Tonn JC, Goldbrunner RH - Brain Pathol. (2008)

Bottom Line: The expression of alpha(v)beta(3) was found to be significantly higher in GBMs than in LGGs, whereby focal strong reactivity was restricted to GBMs only.To further analyze the integrin subunits, Western blots from histologic sections were performed, which demonstrated a significant difference in the expression of the beta(3) integrin subunit between GBMs and LGGs.The presented data lead to new insights in the pattern of alpha(v)beta(3) integrin in gliomas and are of relevance for the inhibition of alpha(v)beta(3) integrin with specific RGD peptides and interfering drugs to reduce angiogenesis and tumor growth.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Klinikum Grosshadern, Ludwig-Maximilians-Universität München, Munich, Germany.

ABSTRACT
In malignant gliomas, the integrin adhesion receptors seem to play a key role for invasive growth and angiogenesis. However, there is still a controversy about the expression and the distribution of alpha(v)beta(3) integrin caused by malignancy. The aim of our study was to assess the extent and pattern of alpha(v)beta(3) integrin expression within primary glioblastomas (GBMs) compared with low-grade gliomas (LGGs). Tumor samples were immunostained for the detection of alpha(v)beta(3) integrin and quantified by an imaging software. The expression of alpha(v)beta(3) was found to be significantly higher in GBMs than in LGGs, whereby focal strong reactivity was restricted to GBMs only. Subsequent analysis revealed that not only endothelial cells but also, to a large extent, glial tumor cells contribute to the overall amount of alpha(v)beta(3) integrin in the tumors. To further analyze the integrin subunits, Western blots from histologic sections were performed, which demonstrated a significant difference in the expression of the beta(3) integrin subunit between GBMs and LGGs. The presented data lead to new insights in the pattern of alpha(v)beta(3) integrin in gliomas and are of relevance for the inhibition of alpha(v)beta(3) integrin with specific RGD peptides and interfering drugs to reduce angiogenesis and tumor growth.

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Hematoxilin & Eosin (H&E) (A) and immunostain of integrin αvβ3 (C), CD31 (D) and fluorescent overlay (B) in samples of glioblastoma. Standard H&E staining (A) shows typical morphology of a malignant glioma. Immunohistochemical staining of αvβ3 (C) is intense in vascular structures (asterisk) as confirmed by a consecutive section stained for the endothelial cell marker CD31 (D). Rather, αvβ3 is clearly detectable throughout the whole section as expressed by the glial tumor cells (arrow). A fluorescent overlay picture of another area with dense tumor growth (B) demonstrates that the integrin αvβ3 (green) is not restricted to vascular structures (red, asterisk) but shows a ubiquitous distribution pattern (cell nuclei blue). Scale bars: 100 µm. Abbreviations: EP = endothelial proliferation; M = mitosis.
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fig01: Hematoxilin & Eosin (H&E) (A) and immunostain of integrin αvβ3 (C), CD31 (D) and fluorescent overlay (B) in samples of glioblastoma. Standard H&E staining (A) shows typical morphology of a malignant glioma. Immunohistochemical staining of αvβ3 (C) is intense in vascular structures (asterisk) as confirmed by a consecutive section stained for the endothelial cell marker CD31 (D). Rather, αvβ3 is clearly detectable throughout the whole section as expressed by the glial tumor cells (arrow). A fluorescent overlay picture of another area with dense tumor growth (B) demonstrates that the integrin αvβ3 (green) is not restricted to vascular structures (red, asterisk) but shows a ubiquitous distribution pattern (cell nuclei blue). Scale bars: 100 µm. Abbreviations: EP = endothelial proliferation; M = mitosis.

Mentions: Immunohistochemical staining of αvβ3 integrin was investigated in sections of GBMs (n = 12), diffuse low-grade astrocytomas (n = 4) as well as non-CNS tumors (n = 5). The expression of αvβ3 integrin was found in the microvessels as well as in the glial tumor cells. The majority of αvβ3 expression in glial tumors was located in samples from GBMs, which are characterized by extensive proliferation of pleomorphic glial cells accompanied by microvascular proliferates with branching glomeruloid vessels. A sample of an HE stain is given in Figure 1A. Figure 1C,D demonstrates the immunohistochemical stainings of an area with vital tumor (left) and a hypercellular zone (mid) surrounding the necrotic areas (right). The staining for αvβ3 integrin, shown in Figure 1C, demonstrates a high endothelium-associated expression in this hypercellular zone. This expression is almost identical to the staining of endothelial marker CD31, as demonstrated in Figure 1D (microvascular association). Nevertheless, numerous tumor cells, especially enlarged giant pleomorphic astrocytes, show a strong immunoreactivity for the αvβ3 integrin, too. In other samples or areas with dense tumor growth, the expression of αvβ3 integrin seems to be associated to glial tumor cells as well. A typical sample is demonstrated by an overlay of fluorescent stainings of αvβ3 integrin and CD31 in Figure 1B. The small branched proliferating microvessels marked by CD31 in red are only partially colocalized with the expression of the αvβ3 integrin in green, which is predominantly located in the glial tumor cells (glial association). The nuclei are counterstained in blue. In contrast to the GBMs, a low expression of αvβ3 integrin is found in WHO grade II diffuse astrocytomas, where the staining was more diffuse and only barely associated with the microvessels (Figure 2B).


Expression of integrin alphavbeta3 in gliomas correlates with tumor grade and is not restricted to tumor vasculature.

Schnell O, Krebs B, Wagner E, Romagna A, Beer AJ, Grau SJ, Thon N, Goetz C, Kretzschmar HA, Tonn JC, Goldbrunner RH - Brain Pathol. (2008)

Hematoxilin & Eosin (H&E) (A) and immunostain of integrin αvβ3 (C), CD31 (D) and fluorescent overlay (B) in samples of glioblastoma. Standard H&E staining (A) shows typical morphology of a malignant glioma. Immunohistochemical staining of αvβ3 (C) is intense in vascular structures (asterisk) as confirmed by a consecutive section stained for the endothelial cell marker CD31 (D). Rather, αvβ3 is clearly detectable throughout the whole section as expressed by the glial tumor cells (arrow). A fluorescent overlay picture of another area with dense tumor growth (B) demonstrates that the integrin αvβ3 (green) is not restricted to vascular structures (red, asterisk) but shows a ubiquitous distribution pattern (cell nuclei blue). Scale bars: 100 µm. Abbreviations: EP = endothelial proliferation; M = mitosis.
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Related In: Results  -  Collection

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fig01: Hematoxilin & Eosin (H&E) (A) and immunostain of integrin αvβ3 (C), CD31 (D) and fluorescent overlay (B) in samples of glioblastoma. Standard H&E staining (A) shows typical morphology of a malignant glioma. Immunohistochemical staining of αvβ3 (C) is intense in vascular structures (asterisk) as confirmed by a consecutive section stained for the endothelial cell marker CD31 (D). Rather, αvβ3 is clearly detectable throughout the whole section as expressed by the glial tumor cells (arrow). A fluorescent overlay picture of another area with dense tumor growth (B) demonstrates that the integrin αvβ3 (green) is not restricted to vascular structures (red, asterisk) but shows a ubiquitous distribution pattern (cell nuclei blue). Scale bars: 100 µm. Abbreviations: EP = endothelial proliferation; M = mitosis.
Mentions: Immunohistochemical staining of αvβ3 integrin was investigated in sections of GBMs (n = 12), diffuse low-grade astrocytomas (n = 4) as well as non-CNS tumors (n = 5). The expression of αvβ3 integrin was found in the microvessels as well as in the glial tumor cells. The majority of αvβ3 expression in glial tumors was located in samples from GBMs, which are characterized by extensive proliferation of pleomorphic glial cells accompanied by microvascular proliferates with branching glomeruloid vessels. A sample of an HE stain is given in Figure 1A. Figure 1C,D demonstrates the immunohistochemical stainings of an area with vital tumor (left) and a hypercellular zone (mid) surrounding the necrotic areas (right). The staining for αvβ3 integrin, shown in Figure 1C, demonstrates a high endothelium-associated expression in this hypercellular zone. This expression is almost identical to the staining of endothelial marker CD31, as demonstrated in Figure 1D (microvascular association). Nevertheless, numerous tumor cells, especially enlarged giant pleomorphic astrocytes, show a strong immunoreactivity for the αvβ3 integrin, too. In other samples or areas with dense tumor growth, the expression of αvβ3 integrin seems to be associated to glial tumor cells as well. A typical sample is demonstrated by an overlay of fluorescent stainings of αvβ3 integrin and CD31 in Figure 1B. The small branched proliferating microvessels marked by CD31 in red are only partially colocalized with the expression of the αvβ3 integrin in green, which is predominantly located in the glial tumor cells (glial association). The nuclei are counterstained in blue. In contrast to the GBMs, a low expression of αvβ3 integrin is found in WHO grade II diffuse astrocytomas, where the staining was more diffuse and only barely associated with the microvessels (Figure 2B).

Bottom Line: The expression of alpha(v)beta(3) was found to be significantly higher in GBMs than in LGGs, whereby focal strong reactivity was restricted to GBMs only.To further analyze the integrin subunits, Western blots from histologic sections were performed, which demonstrated a significant difference in the expression of the beta(3) integrin subunit between GBMs and LGGs.The presented data lead to new insights in the pattern of alpha(v)beta(3) integrin in gliomas and are of relevance for the inhibition of alpha(v)beta(3) integrin with specific RGD peptides and interfering drugs to reduce angiogenesis and tumor growth.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Klinikum Grosshadern, Ludwig-Maximilians-Universität München, Munich, Germany.

ABSTRACT
In malignant gliomas, the integrin adhesion receptors seem to play a key role for invasive growth and angiogenesis. However, there is still a controversy about the expression and the distribution of alpha(v)beta(3) integrin caused by malignancy. The aim of our study was to assess the extent and pattern of alpha(v)beta(3) integrin expression within primary glioblastomas (GBMs) compared with low-grade gliomas (LGGs). Tumor samples were immunostained for the detection of alpha(v)beta(3) integrin and quantified by an imaging software. The expression of alpha(v)beta(3) was found to be significantly higher in GBMs than in LGGs, whereby focal strong reactivity was restricted to GBMs only. Subsequent analysis revealed that not only endothelial cells but also, to a large extent, glial tumor cells contribute to the overall amount of alpha(v)beta(3) integrin in the tumors. To further analyze the integrin subunits, Western blots from histologic sections were performed, which demonstrated a significant difference in the expression of the beta(3) integrin subunit between GBMs and LGGs. The presented data lead to new insights in the pattern of alpha(v)beta(3) integrin in gliomas and are of relevance for the inhibition of alpha(v)beta(3) integrin with specific RGD peptides and interfering drugs to reduce angiogenesis and tumor growth.

Show MeSH
Related in: MedlinePlus