Different epidermal growth factor growth responses and receptor levels in human colon carcinoma cell lines

Wan, Chen; McKnight, Mary K.; Brattain, Diane E.; Brattain, Michael G.; Yeoman, Lynn C.

doi:10.1016/0304-3835(88)90226-1

Cited by 51 publications

(26 citation statements)

References 14 publications

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“…Although luminal EGF does not promote mucosal hyperplasia in the intact gut (65), a breach in mucosal integrity facilitates absorption and activity of luminal EGF ( 17) which may potentiate the effects of EGF secreted within the mucosa (10). Indeed, EGF may influence enterocyte proliferation in an autocrine loop (11). EGF is therefore potentially significant for the regulation ofthe gastrointestinal response to injury.…”

Section: Discussionmentioning

confidence: 99%

“…This 53 amino acid polypeptide was originally isolated from mouse submaxillary glands and subsequently from human urine. EGF is present throughout the gastrointestinal tract (9)(10)(11) together with the related peptide TGFa which appears to activate the same receptor ( 12). Furthermore, the mucosal injury produced by peptic ulcer disease or Crohn's disease induces gastrointestinal stem cells to differentiate into an EGF-secreting lineage (10) while peptic ulcer disease may be associated with increased salivary secretion of EGF ( 13).…”

Section: Introductionmentioning

confidence: 99%

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Human enterocyte (Caco-2) migration is modulated in vitro by extracellular matrix composition and epidermal growth factor.

Basson¹,

Modlin²,

Madri³

1992

J. Clin. Invest.

181

131

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The modulation of enterocyte sheet migration was studied using Caco-2 cells, a well-differentiated human colonic cell line. Although Caco-2 cells attached and spread equivalently over collagen types I, III, IV, and V and laminin, migration over laminin was significantly slower than migration over the collagen types. Fibronectin was a poor substrate for attachment, spreading, and migration. Epidermal growth factor (EGF) stimulated migration over laminin but did not alter Caco-2 migration over collagen or fibronectin. This effect was independent of cell proliferation, which was stimulated equivalently on both laminin and collagen I. Expression and organization of cell surface receptors for matrix (integrins) were studied using antibodies specific for f and a integrin subunits. Integrin surface expression was assessed by immunoprecipitation of surface l25i dinated control and EGF-treated cells. fi1 surface pools did not change substantially in any condition studied. al subunit pools were decreased after EGF treatment on collagen I but al pools increased after EGF treatment on laminin. Surface pools of a2 subunits were increased following EGF treatment whether cells were cultured on laminin or collagen I. However, traditional immunofluorescent and laser confocal imaging demonstrated substantial differences in the character of a2 subunit organization between collagen and laminin in the migrating cell front. Furthermore, a functional antibody to the a2 subunit inhibited EGF stimulation of migration over laminin without substantial effects on basal migration over laminin or collagen I. Thus, EGF appears to exert a matrix-specific effect on enterocyte migration by modulation of integrin expression and organization. (J. Clin. Invest. 1992. 90:15-23.)

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Human enterocyte (Caco-2) migration is modulated in vitro by extracellular matrix composition and epidermal growth factor.

Basson¹,

Modlin²,

Madri³

1992

J. Clin. Invest.

181

131

View full text Add to dashboard Cite

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“…Although up to 77% of colon cancers express EGFR, overexpression of the ErbB family proteins is a rare event for colon cancers (7,12). The typical EGFR density in colon carcinoma cells is f0.4 Â 10 4 to 2 Â 10 4 per cell, several orders of magnitude lower than EGFR-amplified breast cancer cells (13). On the other hand, coexpression of EGFR and its ligand transforming growth factor-a (TGF-a) in colon carcinomas was seen in early-stage disease.…”

Section: Introductionmentioning

confidence: 99%

Synergy of Epidermal Growth Factor Receptor Kinase Inhibitor AG1478 and ErbB2 Kinase Inhibitor AG879 in Human Colon Carcinoma Cells Is Associated with Induction of Apoptosis

Zhou

Brattain

2005

Cancer Research

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Previous studies have shown that constitutive activation of epidermal growth factor receptor (EGFR) and ErbB2 by elevated autocrine transforming growth factor-A (TGF-A) expression plays an important role in colon cancer progression. Coexpression of EGFR and ErbB2 is found in a subset of colon cancers and may cooperatively promote cancer cell growth and survival, as heterodimerization is known to provide for diversification of signal transduction. In this study, the EGFR-selective tyrosine kinase inhibitor (TKI) AG1478 inhibited cell growth of an aggressive human colon carcinoma cell line, FET6AS26X, which harbors constitutively activated EGFR after stable transfection with TGF-A cDNA. However, AG1478 failed to induce apoptosis in FET6AS26X cells at concentrations sufficient for cell growth inhibition and complete suppression of EGFR phosphorylation. Similarly, AG879, a selective ErbB2 TKI, was incapable of inducing apoptosis in FET6AS26X cells at concentrations sufficient to inhibit cell growth and ErbB2 phosphorylation. To test the hypothesis that targeting both ErbB family members would show better efficacy than targeting the single receptors, combinations of inhibitors at fixed ratios of 1:1, 5:1, and 10:1 of AG1478 and AG879, respectively, were compared with single drugs for inhibition of cell growth. All combinations resulted in synergistic effects as indicated by combination index analysis. Synergistic inhibition was associated with induction of apoptosis as reflected by poly(ADP-ribose) polymerase cleavage, caspase-3 activation, and Annexin V staining. Finally, Western blot analysis showed significant inhibition of phosphorylation of both EGFR and ErbB2 by the combination treatment. These data suggest that the strategy to target both EGFR and ErbB2 simultaneously might result in more efficient inhibition of tumor growth than to target single receptor alone. (Cancer Res 2005; 65(13): 5848-56)

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“…In this context, our group has shown that vandetanib possesses antiproliferative antitumor activity in vitro, which acts in a sequence-dependent manner with chemotherapeutic agents, such as oxaliplatin and irinotecan, in two human colon cancer cell lines (27). 5 In that study, treatment with chemotherapeutic agents followed by vandetanib resulted in enhanced antitumor activity in vitro. This effect was completely abrogated by the reverse sequence and/or the concurrent schedule of treatment with chemotherapy and vandetanib (27).…”

mentioning

confidence: 98%

Investigation of Two Dosing Schedules of Vandetanib (ZD6474), an Inhibitor of Vascular Endothelial Growth Factor Receptor and Epidermal Growth Factor Receptor Signaling, in Combination with Irinotecan in a Human Colon Cancer Xenograft Model

Troiani¹,

Serkova²,

Gustafson

et al. 2007

Clinical Cancer Research

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Purpose: This in vivo study was designed to determine the optimal doses and schedules of vandetanib, a dual epidermal growth factor receptor (EGFR)-vascular endothelial growth factor receptor tyrosine kinase inhibitor, in combination with irinotecan in a murine xenograft model of human colon cancer. Experimental Design: HT-29 tumor-bearing nude mice were treated with two doses of vandetanib (12.5 and 25 mg/kg/d) with or without irinotecan (100 mg/kg) using either sequential or concurrent schedules for 30 days. Tumor size was measured using standard variables, whereas the antiangiogenic response was evaluated using dynamic contrast-enhanced magnetic resonance imaging. Additionally, effects on EGFR-dependent signal transduction pathways and proliferation were assessed using immunohistochemistry. These pharmacodynamic end points were then evaluated for associations with antitumor efficacy and/or to plasma/tumor concentrations of vandetanib. Results: The greatest antitumor efficacy was observed in the groups receiving the highest dose of vandetanib given continuously (concurrent schedule), alone or in combination with irinotecan. These dosing schedules resulted in significant effects on tumor vasculature, with decreased volume transfer constants, area under the curve, and permeability surface factor as well as increased gadolinium clearance after 30 days of treatment. In addition, these groups showed the greatest inhibition of EGFR signaling. Interestingly, tumor concentrations of vandetanib were increased by irinotecan in the concurrent schedule, possibly due to decreased tumor perfusion in this group. Conclusions: These data suggest that higher, sustained concentrations of vandetanib (versus intermittent), alone and in combination with irinotecan, result in optimal antitumor efficacy in this model and may have implications for the design of future clinical studies with this drug.

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Different epidermal growth factor growth responses and receptor levels in human colon carcinoma cell lines

Cited by 51 publications

References 14 publications

Human enterocyte (Caco-2) migration is modulated in vitro by extracellular matrix composition and epidermal growth factor.

Human enterocyte (Caco-2) migration is modulated in vitro by extracellular matrix composition and epidermal growth factor.

Synergy of Epidermal Growth Factor Receptor Kinase Inhibitor AG1478 and ErbB2 Kinase Inhibitor AG879 in Human Colon Carcinoma Cells Is Associated with Induction of Apoptosis

Investigation of Two Dosing Schedules of Vandetanib (ZD6474), an Inhibitor of Vascular Endothelial Growth Factor Receptor and Epidermal Growth Factor Receptor Signaling, in Combination with Irinotecan in a Human Colon Cancer Xenograft Model

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