In vitro invasion of small-cell lung cancer cell lines correlates with expression of epidermal growth factor receptor

Damstrup, Lars; Voldborg, B Rude; Spang‐Thomsen, Mogens; Brünner, Nils; Poulsen, Hans Skovgaard

doi:10.1038/bjc.1998.553

Cited by 29 publications

(23 citation statements)

References 36 publications

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“…13 We also demonstrated that all SCLC cell lines expressed several matrix metalloproteases able to degrade components of the basement membrane. However, an expression pattern of these enzymes, which could distinguish EGFR-positive from EGFR-negative SCLC cell lines could not be established, indicating that several mechanisms were involved in conferring in vitro invasion of SCLC cell lines.…”

Section: Discussionmentioning

confidence: 62%

“…We used the EGFR-negative SCLC cell line, GLC3, as a negative control and the EGFR-positive SCLC cell line, CPH54A, as positive control. 13 …”

Section: In Vitro Invasionmentioning

confidence: 99%

“…9 -12 In vitro and in vivo studies have shown that presence of the EGFR strongly correlates to either invasion or increase in formation of lung metastasis. 13,14 In these studies, the EGFR was either stimulated by exogenous EGF 14 or was stimulated by an autocrine loop. 13 Apart from the wild-type EGFR, several deletions and mutations have been described.…”

mentioning

confidence: 99%

“…13,14 In these studies, the EGFR was either stimulated by exogenous EGF 14 or was stimulated by an autocrine loop. 13 Apart from the wild-type EGFR, several deletions and mutations have been described. Of these, deletions in the extracellular domain have been the focus of study in recent years.…”

mentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 62%

“…We used the EGFR-negative SCLC cell line, GLC3, as a negative control and the EGFR-positive SCLC cell line, CPH54A, as positive control. 13 …”

Section: In Vitro Invasionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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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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“…7 Her2/neu is a well-characterized TAA, 28 which is expressed at high density on the surface of a number of human cancers, [2][3][4] including breast cancer, 29 but its expression in normal tissue is restricted. 30 Several studies have been carried out in murine models 7,31 and humans, 23,32 exploiting the Her2/neu oncoprotein as a target antigen.…”

Section: Discussionmentioning

confidence: 99%

Murine monoclonal anti-idiotypic antibody as a surrogate antigen for human Her-2/neu

Baral¹,

Sherrat²,

Das³

et al. 2001

Int. J. Cancer

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Overexpression of epidermal growth factor receptor in human head and neck squamous carcinoma cell lines correlates with matrix metalloproteinase-9 expression andin vitro invasion

et al. 2000

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Numerous reports have shown an association between overexpression of the epidermal growth factor receptor (EGFR), and poor prognosis in head and neck squamous cell carcinomas (HNSCC), however, the underlying mechanisms are still unclear. In the present study, we set out to determine whether EGFR expression was associated with in vitro invasive capacity in a panel of four established and ten newly derived HNSCC lines. Ten of the cell lines expressed high levels of EGFR as determined by a ligand‐binding assay and dot blot analysis, whereas the remaining four showed weak overexpression or normal levels of EGFR. The ability of cells to invade through Matrigel was found to be higher in the EGFR overexpressing cell lines (p < 0.0001). Expression levels of matrix metalloproteinases (MMP‐1, MMP‐2, MMP‐3, MMP‐7, MMP‐9, MMP‐10, MMP‐11, MMP‐13, MT1‐MMP) and tissue inhibitors of MMP (TIMP‐1, TIMP‐2) were evaluated by semiquantitative RT‐PCR, substrate zymography and western blot. We found a strong positive correlation between EGFR levels and the expression of MMP‐9 mRNA (r2 = 0.95; p < 0.0001), MMP‐9 enzyme activity (r2 = 0.8099; p < 0.0001) and an inverse correlation with TIMP‐1 (r2 = 0.48; p = 0.0059). In six selected HNSCC lines, in vitro invasion was assayed in the presence of an anti‐EGFR monoclonal antibody, ICR62. A significant reduction of invasion in four selected EGFR‐overexpressing cell lines was found with 30 nM ICR62 (from 50% to 70%; p < 0.001) but there was no effect in two cell lines with normal EGFR levels. Our results show that the in vitro invasive phenotype of HNSCC lines correlates with high EGFR and MMP‐9 expression, and it is therefore suggested that the EGFR signaling pathway might play an important role in the invasive behavior of HNSCC via specific upregulation of MMP‐9 and downregulation of TIMP‐1. Int. J. Cancer 86:307–317, 2000. © 2000 Wiley‐Liss, Inc.

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In vitro invasion of small-cell lung cancer cell lines correlates with expression of epidermal growth factor receptor

Cited by 29 publications

References 36 publications

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

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

Murine monoclonal anti-idiotypic antibody as a surrogate antigen for human Her-2/neu

Overexpression of epidermal growth factor receptor in human head and neck squamous carcinoma cell lines correlates with matrix metalloproteinase-9 expression andin vitro invasion

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