Epidermal growth factor (EGF)- and transforming growth factor alpha-stimulated invasion and growth of follicular thyroid cancer cells can be blocked by antagonism to the EGF receptor and tyrosine kinase in vitro

Hölting, T; Siperstein, Allan; Clark, Orlo H.; Duh, Quan‐Yang

doi:10.1530/eje.0.1320229

Cited by 56 publications

(30 citation statements)

References 18 publications

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“…Our present results closely agree with our previous work (41) and other studies (42) reporting that EGFR is overexpressed in differentiated and anaplastic thyroid carcinomas and that targeting EGFR by anti-EGFR antibodies (EGFR antibody 528) completely neutralized the EGF-mediated stimulation of FTC cell growth and invasion in culture (19). Furthermore, our findings agree with studies showing that genistein, a general tyrosine kinase antagonist, can abrogate growth stimulation of EGF and transforming growth factor-a (TGF-a) on invasion and growth of FTC cells (19).…”

Section: Discussionsupporting

confidence: 93%

“…Furthermore, our findings agree with studies showing that genistein, a general tyrosine kinase antagonist, can abrogate growth stimulation of EGF and transforming growth factor-a (TGF-a) on invasion and growth of FTC cells (19).…”

Section: Discussionsupporting

confidence: 91%

“…The EGF and EGFR are overexpressed in thyroid carcinomas in comparison with normal thyroid tissue (18). EGF stimulates the growth, proliferation, and invasion of FTC cells and the blockade of EGFR signaling decreases the growth and invasion of FTC cells in vitro (19). In fact, high expression of EGFR is associated with poor prognosis in thyroid tumors (18).…”

Section: Introductionmentioning

confidence: 99%

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Antivascular Therapy of Human Follicular Thyroid Cancer Experimental Bone Metastasis by Blockade of Epidermal Growth Factor Receptor and Vascular Growth Factor Receptor Phosphorylation

Younes¹,

Yigitbasi²,

Park³

et al. 2005

Cancer Research

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Patients suffering from bone metastases of follicular thyroid carcinoma (FTC) have a poor prognosis because of the lack of effective treatment strategies. The overexpression of epidermal growth factor receptor (EGFR) associated with increased vascularity has been implicated in the pathogenesis of FTC and subsequent bone metastases. We hypothesized that inhibiting the phosphorylation of the EGFR and vascular endothelial growth factor receptor (VEGFR) by AEE788, a dual tyrosine kinase inhibitor of EGFR and VEGFR, in combination with paclitaxel would inhibit experimental FTC bone lesions and preserve bone structure. We tested this hypothesis using the human WRO FTC cell line. In culture, AEE788 inhibited the EGF-mediated phosphorylation of EGFR, VEGFR2, mitogen-activated protein kinase, and Akt in culture. AEE788, alone and in combination with paclitaxel, inhibited cell growth and induced apoptosis. When WRO cells were injected into the tibia of nude mice, tumor and endothelial cells within the lesions expressed phosphorylated EGFR, VEGFR, Akt, and mitogenactivated protein kinase that were inhibited by the oral administration of AEE788. Therapy consisting of orally given AEE788 and i.p. injected paclitaxel induced a high level of apoptosis in tumor-associated endothelial cells and tumor cells with the inhibition of tumor growth in the bone and the preservation of bone structure. Collectively, these data show that blocking the phosphorylation of EGFR and VEGFR with AEE788 combined with paclitaxel can significantly inhibit experimental human FTC in the bone of nude mice. (Cancer Res 2005; 65(11): 4716-27)

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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Antivascular Therapy of Human Follicular Thyroid Cancer Experimental Bone Metastasis by Blockade of Epidermal Growth Factor Receptor and Vascular Growth Factor Receptor Phosphorylation

Younes¹,

Yigitbasi²,

Park³

et al. 2005

Cancer Research

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“…Our observations also have significant implications for the spread of epithelial tumors that commonly express ␣v␤5 (53). In this regard, it is particularly interesting that the autocrine production of TGF-␣ has been linked to both the expression of malignancy and motility in carcinomas (54). While the precise mechanism of uPA⅐uPAR in cell migration is not completely understood, it appears that this ligand-receptor complex functionally cooperates with integrin ␣v␤5 to promote the migration of carcinoma cells.…”

Section: Figmentioning

confidence: 70%

Requirement of Receptor-bound Urokinase-type Plasminogen Activator for Integrin αvβ5-directed Cell Migration

Yebra

Parry

Strömblad

et al. 1996

Journal of Biological Chemistry

237

147

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The urokinase plasminogen activator (uPA) interacts with its cell surface receptor (uPAR), providing an inducible, localized cell surface proteolytic activity, thereby promoting cellular invasion. Evidence is provided for a novel function of cell surface-associated uPA⅐uPAR. Specifically, induction of cell surface expression of uPA⅐uPAR by growth factors or phorbol ester was necessary for vitronectin-dependent carcinoma cell migration, an event mediated by integrin ␣v␤5. Cell migration on vitronectin was blocked with either a soluble form of uPAR, an antibody that disrupts uPA binding to uPAR, or a monoclonal antibody to ␣v␤5. Moreover, plasminogen activator inhibitor type 2 blocked this migration event but did not affect adhesion, suggesting a direct role for uPA enzyme activity in this process and that migration but not adhesion of these cells is regulated by uPA⅐uPAR. Growth factor-mediated induction of uPA⅐uPAR on the carcinoma cell surface promotes a specific motility event mediated by integrin ␣v␤5, since cells transfected with the ␤3 integrin subunit expressed ␣v␤3 and migrated on vitronectin independently of growth factors or uPA⅐uPAR expression. This relationship between ␣v␤5 and the uPA⅐uPAR system has significant implications for regulation of motility events associated with development, angiogenesis, and tumor metastasis.

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“…46 The v-erbA oncogene coding for a truncated thyroid hormone receptor has been shown to cooperate with platelet-derived growth factor to increase in vitro invasion. 47 In other cell types a role for the EGFR has also been demonstrated; for example, Hölting et al 48 showed that in a follicular thyroid cancer cell line EGF or TGF-␣ stimulated invasion over unstimulated cells (p Ͻ 0.02). Similar results were found by Hamada et al 49 in rat mammary carcinoma cells in which EGF stimulated in vitro invasion in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 98%

Epidermal growth factor receptor mutation type iii transfected into a small cell lung cancer cell line is predominantly localized at the cell surface and enhances the malignant phenotype

Damstrup

Pedersen

Bastholm

et al. 2001

Intl Journal of Cancer

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In the present study we transfected the epidermal growth factor receptor (EGFR)-negative small cell lung cancer cell line, GLC3, with the type III EGFR mutation (EGFRvIII). The EGFRvIII protein could be detected by Western blot analysis as a 145-kDa protein, which by immunohistochemistry appeared to be localized at the cell surface. Ultrastructurally EGFRvIII was expressed mainly at the cell surface with clusters at cell-cell contacts. In the in vitro invasion assay, GLC3-EGFRvIII cells had a Ϸ5-fold increased invasion compared with uninduced GLC3-EGFRvIII, GLC3-Tet-On and the parental cell line. GLC3-Tet-On appeared uniform in size with adherence junctions at cell-cell contacts. In uninduced GLC3-EGFRvIII cells adherence junctions were also present but less distinct. In doxycycline-pretreated GLC3-EGFRvIII cells, adherence junctions were absent. We conclude that the expression of EGFRvIII results in a more malignant phenotype. This effect appears to involve the disruption of adherence junctions.

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Epidermal growth factor (EGF)- and transforming growth factor alpha-stimulated invasion and growth of follicular thyroid cancer cells can be blocked by antagonism to the EGF receptor and tyrosine kinase in vitro

Cited by 56 publications

References 18 publications

Antivascular Therapy of Human Follicular Thyroid Cancer Experimental Bone Metastasis by Blockade of Epidermal Growth Factor Receptor and Vascular Growth Factor Receptor Phosphorylation

Antivascular Therapy of Human Follicular Thyroid Cancer Experimental Bone Metastasis by Blockade of Epidermal Growth Factor Receptor and Vascular Growth Factor Receptor Phosphorylation

Requirement of Receptor-bound Urokinase-type Plasminogen Activator for Integrin αvβ5-directed Cell Migration

Epidermal growth factor receptor mutation type iii transfected into a small cell lung cancer cell line is predominantly localized at the cell surface and enhances the malignant phenotype

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