Platelet-derived Growth Factor Signaling and Human Cancer

Yu, Jiuhong; Ustach, Carolyn V.; Kim, Hyeong Reh Choi

doi:10.5483/bmbrep.2003.36.1.049

Cited by 197 publications

(198 citation statements)

References 96 publications

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“…Cytokines such as vascular endothelial cell growth factors, TGFs, FGFs, plateletderived growth factors, monocyte chemoattractant protein-1, and IL-8 released from the neoplasm or inflammatory tissue are all possible candidates. 27,[30][31][32][33][34] It is known that these factors released from cancer cells promote the migration of endothelial cell and stromal cell progenitors from the bone marrow towards the cancer bed 35,36 or tissue surrounding the tumor, enhancing the formation of tumor-stroma. 37 Similar mechanisms would be anticipated for tumor-stromal formation in glioma, and for the migration of implanted MSCs.…”

Section: Discussionmentioning

confidence: 99%

Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model

et al. 2004

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The prognosis of patients with malignant glioma is extremely poor, despite the extensive surgical treatment that they receive and recent improvements in adjuvant radio-and chemotherapy. In the present study, we propose the use of gene-modified mesenchymal stem cells (MSCs) as a new tool for gene therapy of malignant brain neoplasms. Primary MSCs isolated from Fischer 344 rats possessed excellent migratory ability and exerted inhibitory effects on the proliferation of 9L glioma cell in vitro. We also confirmed the migratory capacity of MSCs in vivo and showed that when they were inoculated into the contralateral hemisphere, they migrated towards 9L glioma cells through the corpus callosum. MSCs implanted directly into the tumor localized mainly at the border between the 9L tumor cells and normal brain parenchyma, and also infiltrated into the tumor bed. Intratumoral injection of MSCs caused significant inhibition of 9L tumor growth and increased the survival of 9L glioma-bearing rats. Gene-modification of MSCs by infection with an adenoviral vector encoding human interleukin-2 (IL-2) clearly augmented the antitumor effect and further prolonged the survival of tumor-bearing rats. Thus, gene therapy employing MSCs as a targeting vehicle would be promising as a new therapeutic approach for refractory brain tumor.

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Section: Discussionmentioning

confidence: 99%

Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model

et al. 2004

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“…Platelet-derived growth factor exerts its biological activity by binding to structurally similar a-or b-PDGFRs. Ligand-induced receptor dimerisation leads to increased tyrosine kinase activity, triggering PDGF signal transduction molecules such as phosphatidylinositol 3-kinase (PI3K)/Akt kinase (Yu et al, 2003). The importance of PDGF signalling in malignant gliomas is demonstrated by recent investigation that PDGF autocrine stimulation in the brain of neonatal mice results in the formation of gliomas (Uhrbom et al, 1998).…”

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confidence: 99%

Inhibition of platelet-derived growth factor signalling induces autophagy in malignant glioma cells

et al. 2004

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Malignant gliomas highly coexpress platelet-derived growth factor (PDGF) and its receptor, suggesting the presence of an autocrine loop. Therefore, disruption of PDGF ligand/receptor complex represents a promising strategy for the treatment of malignant gliomas. However, the mechanisms of the antitumour effect exerted by the inhibition of PDGF-mediated cell growth remain unclear. In the present study, using anti-PDGF neutralising antibody, we investigated the effect of the inhibition of PDGF signalling on malignant glioma U87-MG, D54, and T98G cells with high levels of PDGF-A and -B. As a control, normal fibroblast MRC5 cells expressing low levels of PDGF-A and -B were used. Treatment with anti-PDGF neutralising antibody did not affect the expressions of PDGF-A, PDGF-B, and Akt, but suppressed the level of phosphorylated Akt in tumour cells, indicating the inhibition of PDGF signalling. The cell viability of all malignant glioma cells tested in this study was significantly inhibited in a time-dependent manner following the treatment compared to that of fibroblast cells (Po0.02 to o0.05). The antitumour effect of anti-PDGF antibody was suppressed by the activation of Akt and enhanced by the downregulation of Akt. Interestingly, the inhibition of PDGF signalling induced the development of acidic vesicular organelles and the autophagosome membrane association of the microtubule-associated protein light chain 3, which are characteristic of autophagy, in malignant glioma cells, while apoptotic cell death was not observed. Together these findings imply a new concept of autophagy for PDGF autocrine inhibition in malignant gliomas.

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“…Also, members of the platelet-derived growth factor (PDGF) family can promote angiogenesis as disulphide-linked heterodimers (PDGF-AB) or homodimers (PDGF-AA, PDGF-BB, PDGF-CC and PDGF-DD) (Yu et al, 2003). Moreover, the chemokines CXCL1, -2, -3, -5, -6, -7 and -8 can exert angiogenic activity (Strieter et al, 2006).…”

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confidence: 99%

Angiogenesis and lymphangiogenesis are downregulated in primary breast cancer

et al. 2009

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BACKGROUND: Angiogenesis and lymphangiogenesis are considered to play key roles in tumour growth, progression and metastasis. However, targeting tumour angiogenesis in clinical trials showed only modest efficacy. We therefore scrutinised the concept of tumour angiogenesis and lymphangiogenesis by analysing the expression of crucial markers involved in these processes in primary breast cancer. METHODS: We analysed the expression of angiogenic, lymphangiogenic or antiangiogenic factors, their respective receptors and specific markers for endothelial and lymphendothelial cells by quantitative real-time RT-PCR in primary breast cancer and compared the expression profiles to non-cancerous, tumour-adjacent tissues and breast tissues from healthy women. RESULTS: We found decreased mRNA amounts of major angiogenic and lymphangiogenic factors in tumour compared to healthy tissues, whereas antiangiogenic factors were upregulated. Concomitantly, angiogenic and lymphangiogenic receptors were downregulated in breast tumours. This antiangiogenic, antilymphangiogenic microenvironment was even more pronounced in aggressive tumours and accompanied by reduced amounts of endothelial and lymphatic endothelial cell markers. CONCLUSION: Primary breast tumours are not a site of highly active angiogenesis and lymphangiogenesis. Selection for tumour cells that survive with minimal vascular supply may account for this observation in clinical apparent tumours.

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Platelet-derived Growth Factor Signaling and Human Cancer

Cited by 197 publications

References 96 publications

Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model

Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model

Inhibition of platelet-derived growth factor signalling induces autophagy in malignant glioma cells

Angiogenesis and lymphangiogenesis are downregulated in primary breast cancer

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