Melanoma-associated expression of vascular endothelial growth factor and its receptors FLT-1 and KDR

Graeven, Ullrich; Fiedler, Walter; Karpinski, Sonja; Ergün, Süleyman; Kilic, Nerbil; Rodeck, Ulrich; Schmiegel, Wolff; Hossfeld, Dieter K.

doi:10.1007/s004320050325

Cited by 83 publications

(80 citation statements)

References 31 publications

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“…Angiogenesis and melanoma M Streit and M Detmar these studies demonstrated that VEGF expression is not as prominent in melanomas as in most epithelial cancers (Dvorak et al, 1995) and, therefore, might not represent the major angiogenic activity in these tumors, the expression of functional VEGF receptors on human melanoma cells suggests the intriguing possibility that VEGF might also exert autocrine effects on the tumor cells themselves (Gitay-Goren et al, 1993;Liu et al, 1995;Graeven et al, 1999;Lacal et al, 2000). Expression of mRNA for basic fibroblast growth factor (bFGF, FGF-2), a potent angiogenesis factor, has been detected in metastatic and primary invasive melanomas, whereas melanocytes in benign nevi did not express this factor (Reed et al, 1994) .…”

Section: Expression Of Angiogenesis Modulators By Human Melanomasmentioning

confidence: 99%

Angiogenesis, lymphangiogenesis, and melanoma metastasis

Streit¹,

2003

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The induction of angiogenesis is a critical point in the development of most human tumors -including melanomas. Some of the earliest studies in the field of tumor angiogenesis showed that transplantation of human melanoma fragments into the hamster cheek pouch stimulated blood vessel growth. Since then, numerous studies have demonstrated that human melanomas also induce angiogenesis. The prognostic importance of the degree of melanoma vascularization, however, has remained controversial. Elevated expression of several angiogenic factors, including vascular endothelial growth factor, basic fibroblast growth factor, and interleukin-8, has been detected in primary cutaneous melanomas, and the importance of these mediators in promoting melanoma angiogenesis and metastasis has been confirmed in tumor xenotransplant models. Based upon these findings, several clinical trials of angiogenesis inhibitors have been initiated in human melanoma patients and are currently underway. Recent experimental evidence indicates that tumorassociated lymphangiogenesis also plays an important role in mediating tumor spread to regional lymph nodes. These observations have important implications for prognosis and treatment of human melanomas.

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Section: Expression Of Angiogenesis Modulators By Human Melanomasmentioning

confidence: 99%

Angiogenesis, lymphangiogenesis, and melanoma metastasis

Streit¹,

2003

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“…Moreover, clinical studies have shown that PlGF levels of expression in tumour cells correlate with poor prognosis in various tumours types (1,2). In human melanoma cell lines, the expression of this cytokine and of VEGFR-1 has been described, and a correlation between PlGF expression and tumour progression has been suggested (10)(11)(12)(13)(14).…”

Section: Discussionmentioning

confidence: 99%

“…We previously demonstrated the co-expression of PlGF and VEGFR-1 in a large number of human melanoma cell lines (10) and, together with other groups, suggested that the interaction of PlGF with VEGFR-1 might modulate cellular pathways important for melanoma cell proliferation, apoptosis and invasiveness (10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 87%

Placenta growth factor induces melanoma resistance to temozolomide through a mechanism that involves the activation of the transcription factor NF-κB

et al. 2010

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Abstract. Placenta growth factor (PlGF) and its receptor vascular endothelial growth factor receptor-1 (VEGFR-1) are co-expressed in a large number of human melanoma cell lines. Moreover, a correlation between in vivo PlGF production and melanoma progression has been suggested. To investigate whether PlGF might have a role in protecting melanoma cells from the cytotoxic effects of the anticancer agent temozolomide (TMZ), which is used for the treatment of this malignancy, we stably transfected a doxycyclineinducible PlGF antisense mRNA into a human melanoma cell clone that secretes VEGF-A and PlGF and expresses receptors for both growth factors. Induction of PlGF antisense mRNA in the transfected cells (13443/ASP3 subclone) halved TMZ IC 50 , and exogenous addition of PlGF to the culture medium 24 h before TMZ treatment, partially restored IC 50 values to that of control cells. The increased sensitivity of 13443/ASP3 cells upon PlGF antisense mRNA expression was not due to down-regulation of O 6 -methylguanine-DNA methyltransferase, a DNA repair protein that represents the main mechanism of resistance to TMZ. Since the activity of the transcription factor nuclear factor-κB (NF-κB) has been correlated to melanoma chemoresistance, we investigated whether NF-κB was involved in PlGF-induced melanoma cell resistance to TMZ. Induction of PlGF antisense mRNA in 13443/ASP3 cells halved the levels of active NF-κB and the specific inhibition of this transcription factor increased sensitivity of 13443/ASP3 cells to TMZ. In conclusion, our data strongly suggest that PlGF plays a role in melanoma cell resistance to TMZ through a pathway that involves NF-κB activation.

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“…Melanoma cells have been shown to secrete VEGF and angiogenesis has been demonstrated in uveal melanoma and its metastasis. 2,3 It has been speculated that inhibition of VEGF may diminish the metastatic potential by avoiding angiogenesis, providing a possible role for bevacizumab. 23 However, a large variation of tumour VEGF expression has been reported in uveal melanoma and expression of VEGF may correlate with poor prognosis.…”

Section: Animal Modelsmentioning

confidence: 99%

“…VEGF levels have been demonstrated to be elevated in choroidal melanoma. 2,3 However, the use of anti-angiogenic agents such as bevacizumab -a recombinant humanised anti-VEGF monoclonal antibody -has not been extensively investigated for the treatment of choroidal melanoma.…”

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confidence: 99%

Bevacizumab Therapy for Choroidal Melanoma

Lima¹,

Singh²

2012

European Oncology &Amp; Haematology

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Bevacizumab, an anti-angiogenic agent, has gained widespread use in ophthalmology for the treatment of neovascular conditions, such as age-related macular degeneration. Targeting angiogenesis has been proposed as a potential therapy for different kinds of malignancies, by limiting supply of oxygen and nutrients, and consequently tumour growth and metastasis. Bevacizumab has been approved by the US Food and Drug Administration, along with chemotherapy, for the treatment of metastatic colorectal carcinoma and non-small cell lung cancer. Nevertheless, a beneficial effect in the treatment of choroidal melanoma has yet to be demonstrated, despite elevated levels of vascular endothelial growth factor (VEGF). However, bevacizumab might have a role in the management of complications of radiation therapy. KeywordsBevacizumab, choroidal melanoma, optic neuropathy, radiation retinopathy, vascular endothelial growth factor (VEGF) Disclosure: The authors have no conflicts of interest to declare. The impact of intravitreal bevacizumab as a primary therapy for choroidal melanoma and its role in the management of complications (e.g., radiation retinopathy) from established therapies (e.g., brachytherapy) will be discussed here. Results from animal models, in which bevacizumab has been used either systemically or intravitreally, will be reviewed. Current clinical trials looking at the administration of intravitreal or systemic anti-VEGF agents for choroidal melanoma will be summarised. Treatment of Primary TumourIntravitreal bevacizumab, along with other anti-VEGF agents, has gained widespread use in ophthalmology over the last few years for the treatment of neovascular diseases, such as age-related macular degeneration, central retinal vein occlusion, proliferative diabetic retinopathy and macular oedema. It has been shown to reduce neovascular activity and vascular permeability in ocular tissues. It is that of a 55-year-old woman who presented for further investigation of a peripapillary choroidal lesion presumed to be an idiopathic choroidal neovascular membrane, and who was treated with five intravitreal injections of bevacizumab at monthly intervals.Choroidal melanoma has intrinsic vessels and commonly has associated subretinal fluid. Bevacizumab may transiently diminish tumour vasculature and permeability, reducing the subretinal fluid.However, subretinal fluid resolution may be misleading in this scenario and the tumour may to continue to grow. 8In the absence of studies documenting the efficacy of bevacizumab for the treatment of choroidal melanoma, caution is advised in the use of this drug as a sole treatment modality. Management of ComplicationsSince the Collaborative ocular melanoma study (COMS), therapy for medium-sized choroidal melanomas has shifted from enucleation to plaque brachytherapy, as the survival rate has been found to be similar. 7Radiation retinopathy, optic neuropathy, iris neovascularisation and neovascular glaucoma are potential complications of plaque

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Melanoma-associated expression of vascular endothelial growth factor and its receptors FLT-1 and KDR

Cited by 83 publications

References 31 publications

Angiogenesis, lymphangiogenesis, and melanoma metastasis

Angiogenesis, lymphangiogenesis, and melanoma metastasis

Placenta growth factor induces melanoma resistance to temozolomide through a mechanism that involves the activation of the transcription factor NF-κB

Bevacizumab Therapy for Choroidal Melanoma

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