Immunohistochemistry with antibodies to hepatocyte growth factor and its receptor protein (c-MET) in human brain tissues

Yamada, Tatsuo; Tsubouchi, Hirohito; Daikuhara, Yasushi; Prat, María; Comoglio, Paolo M.; McGeer, P. L.; McGeer, Edith G.

doi:10.1016/0006-8993(94)91250-5

Cited by 70 publications

(47 citation statements)

References 13 publications

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“…Whereas in situ hybridization studies on mammalian brain did not detect MET mRNA expression in microglial cells (Jung et al, 1994), immunohistochemical analysis showed MET protein on neurons as well as microglial cells (Di Renzo et al, 1993;Yamada et al, 1994). Such discrepancies could be due to variations in mRNA stability or differences in posttranscriptional regulation.…”

Section: Discussionmentioning

confidence: 99%

Expression and localization of scatter factor/hepatocyte growth factor in human astrocytomas

Kunkel¹,

Müller²,

Schirmacher³

et al. 2001

Neuro-Oncol

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Scatter factor/hepatocyte growth factor (SF/HGF) is a pleiotropic cytokine that has been implicated in glioma invasion and angiogenesis. The SF/HGF receptor, MET, has been found to be expressed in neoplastic astrocytes as well as in endothelial cells of the tumor vasculature. Both SF/HGF and MET expression have also been described to correlate with the malignancy grade of human gliomas. However, most glioblastoma cell lines lack SF/HGF expression, raising the question of the cellular origin of SF/HGF in vivo. Using in situ hybridization, we analyzed glioblastomas, anaplastic astrocytomas, diffuse astrocytomas, pilocytic astrocytomas, and normal brain for the expression of SF/HGF mRNA. We detected strong SF/HGF expression by the majority of the tumor cells and by vascular endothelial cells in all glioblastoma specimens analyzed. Combined use of in situ hybridization with uorescence immunohistochemistry con rmed the astrocytic origin of the SF/HGF-expressing cells. In contrast, CD68-immunoreactive microglia/macrophages, as well as vascular smooth muscle cells reactive to a -smooth muscle actin, lacked SF/HGF expression. In anaplastic, diffuse, and pilocytic astrocytomas, SF/HGF expression was con ned to a subset of tumor cells, and signals were less intense than in glioblasto mas. In addition, we detected SF/HGF mRNA in cortical neurons. SF/HGF expression was not up regulated around necroses or at tumor margins. MET immunoreactivity was observed in GFAP-expressing astrocytic tumor cells and endothelial cells as well as in a subset of microglia/macrophages. We conclude that in vivo, both autocrine and paracrine stimulation of tumor cells and endothelium through the SF/HGF-MET system are likely to contribute to tumor invasion and angiogenesis. Lack of SF/HGF expression by most cultured glioblastoma cells is not representative of the in vivo situation and most likely represents a culture artifact. Neuro-Oncology 3, 82-88, 2001 (Posted to Neuro-Oncology [serial online], Doc. 00-044, February 19, 2001 S F/HGF 3 stimulates the motility and proliferation of several cancer cell types and can induce angiogenesis (Rosen et al., 1994). Its biologic effects are mediated by the transmembrane tyrosine kinase receptor, MET, which is encoded by the proto-oncogene MET. Several studies suggest that, in gliomas, SF/HGF may function as an important tumor progression factor. We have previously observed a correlation between the concentration of SF/HGF in gliomas with the malignancy grade (Lamszus et al., 1998). Moreover, SF/HGF turned out to be a statistically independent predictive parameter for glioma microvessel density, independent of VEGF (Schmidt et al., 1999). Abbreviations used are as follows: DIG, digoxigenin; GFAP, glial brillary acidic protein; SF/HGF, scatter factor/hepatocyte growth factor; a -SMA, a -smooth muscle actin; SSC, saline-sodium citrate; VEGF, vascular endothelial growth factor. Neuro-Oncology P. Kunkel et al.: SF/HGF expression in astrocytomasNeuro-Oncology n A P R I L 2 0 0 1 83 Glioblastoma cell lines usu...

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Section: Discussionmentioning

confidence: 99%

Expression and localization of scatter factor/hepatocyte growth factor in human astrocytomas

Kunkel¹,

Müller²,

Schirmacher³

et al. 2001

Neuro-Oncol

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“…Expression of HGF gene has been reported in the normal brain tissue, particularly in neurons [16]. Immunohistochemically, HGF and its receptor c-Met protein were reported to be positive in astrocytes and microglia, respectively [14,15]. Amplification of c-met gene has recently been described in glioblastoma cell line and tissues [27][28][29], however, expression of HGF and c-met mRNAs in glioma has yet been clarified so far.…”

Section: Discussionmentioning

confidence: 99%

Concomitant expression of hepatocyte growth factor (HGF), HGF activator and c‐met genes in human glioma cells in vitro

et al. 1995

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“…Both HGF and c-Met have been identified in brain astrocytes, microglial cells, and astrocytic tumors. [35][36][37] In astrocytic tumor cells, the expression levels of HGF and c-Met correlates with the grade of malignancy, 38,39 and HGF supplementation to cultures enhances the invasiveness of glioma cells while it does not alter their mitogenesis. 40 The present results obtained on Mü ller cells are in agreement with data obtained on cultured brain astrocytes, which revealed that HGF promotes chemokinesis without an influence on mitogenesis.…”

Section: Discussionmentioning

confidence: 99%

Glial cell expression of hepatocyte growth factor in vitreoretinal proliferative disease

Hollborn

Krausse

Iandiev

et al. 2004

Laboratory Investigation

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The hepatocyte growth factor (HGF) has been crucially implicated in the development of proliferative retinal diseases; however, it is unclear whether retinal glial cells express or respond to HGF. Therefore, we examined the expression of HGF and of the receptor for HGF, c-Met, by immunohistochemical costaining with glial fibrillary acidic protein (GFAP) in epiretinal membranes of patients with proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR), respectively. Furthermore, it was determined whether cells of the human retinal glial cell line, MIO-M1, secrete HGF protein, and whether HGF stimulates proliferation and chemotaxis, and secretion of the vascular endothelial growth factor (VEGF). Neuroretinas of patients with PVR express elevated mRNA level for HGF in comparison to control retinas. In epiretinal membranes of patients with PVR or PDR, immunoreactivity for HGF and for c-Met, respectively, partially colocalized with immunoreactivity for GFAP. Fetal bovine serum and basic fibroblast growth factor, but not heparin-binding epidermal or plateletderived growth factors, evoked HGF secretion by cultured retinal glial cells. HGF displayed only a marginal effect on cell proliferation while it stimulated chemotaxis. HGF promoted the secretion of VEGF, via activation of the phosphatidylinositol-3 kinase. It is concluded that glial cells in epiretinal membranes express both HGF protein and c-Met receptors. The results suggest an autocrine/paracrine role of HGF in glial cell responses during proliferative vitreoretinal disorders as well as in retinal neovascularization, by stimulating of VEGF release.

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Immunohistochemistry with antibodies to hepatocyte growth factor and its receptor protein (c-MET) in human brain tissues

Cited by 70 publications

References 13 publications

Expression and localization of scatter factor/hepatocyte growth factor in human astrocytomas

Expression and localization of scatter factor/hepatocyte growth factor in human astrocytomas

Concomitant expression of hepatocyte growth factor (HGF), HGF activator and c‐met genes in human glioma cells in vitro

Glial cell expression of hepatocyte growth factor in vitreoretinal proliferative disease

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