Effects of EGF and TGF-α on Invasion and Proteinase Expression of Uterine Cervical Adenocarcinoma OMC-4 Cells

Ueda, Masatsugu; Fujii, H.; Yoshizawa, Keiko; Kumagai, Koji; Ueki, Ken; Ueki, Minoru

doi:10.1159/000024510

Cited by 21 publications

(16 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Little is known about the role of MMPs in the progression of thyroid carcinoma; however, MMP-2 activation (with activation ratios similar to those we report) and MT1-MMP expression correlate with the presence of lymph node metastases in papillary thyroid carcinomas (Nakamura et al 1999). Growth factors stimulate MMP-9 release in head and neck squamous cell carcinomas (O-charoenrat et al 2000) and correlate with increased invasiveness in other cancer cell types (Price et al 1996, Ueda et al 1998, Harvey et al 2000. A recent report demonstrated a link between activating mutations in the BRAF oncogene, commonly present in papillary thyroid carcinomas, with the upregulation of MMPs (Mesa et al 2006).…”

Section: Discussionmentioning

confidence: 99%

Differentiated thyroid cancer cell invasion is regulated through epidermal growth factor receptor-dependent activation of matrix metalloproteinase (MMP)-2/gelatinase A

Yeh¹,

Rougier²,

Park³

et al. 2006

Endocr Relat Cancer

View full text Add to dashboard Cite

Mechanisms of invasion in thyroid cancer remain poorly understood. We hypothesized that signaling via the epidermal growth factor receptor (EGFR) stimulates thyroid cancer cell invasion by altering the expression and cleavage of matrix metalloproteinases (MMPs). Papillary and follicular carcinoma cell lines were treated with EGF, the EGFR tyrosine kinase inhibitor AG1478, and the MMP inhibitors GM-6001 and Col-3. Flow cytometry was used to detect EGFR. In vitro invasion assays, gelatin zymography, and quantitative reverse transcription-PCR were used to assess the changes in invasive behavior and MMP expression and activation. All cell lines were found to overexpress functional EGFR. EGF stimulated invasion by thyroid cancer cells up to sevenfold (P!0.0001), a process that was antagonized completely by AG1478 and Col-3, partially by GM-6001, but not by the serine protease inhibitor aprotinin. EGF upregulated expression of MMP-9 (2.64-to 8.89-fold, P!0.0001) and membrane type-1 MMP (MT1-MMP, 1.97-to 2.67-fold, P!0.0001). This effect was blocked completely by AG1478 and partially by Col-3. The activation of MMP-2 paralleled MT1-MMP expression. We demonstrate that MMPs are critical effectors of invasion in the papillary and follicular thyroid cancer cell lines studied. Invasion is regulated by signaling through EGFR, an effect mediated by augmentation of gelatinase expression and activation. MMP inhibitors and growth factor antagonists may be effective tumoristatic agents for the treatment of aggressive thyroid carcinomas.

show abstract

Section: Discussionmentioning

confidence: 99%

Differentiated thyroid cancer cell invasion is regulated through epidermal growth factor receptor-dependent activation of matrix metalloproteinase (MMP)-2/gelatinase A

Yeh¹,

Rougier²,

Park³

et al. 2006

Endocr Relat Cancer

View full text Add to dashboard Cite

show abstract

“…The interaction between LN-5 γ2 and EGFR in vitro was confirmed by this immunohistochemical investigation of squamous cell carcinoma of the tongue. In addition to the above-mentioned direct association between LN-5 γ2 and EGFR, specific kinds of molecules such as MMP-2 may be involved in the interaction between LN-5 γ2 and EGFR [5, 39, 40]. In addition to transcriptional activation of the EGFR gene, our results suggest that EGFR gene amplification and overexpression may not only promote cell proliferation but also the migration of tumor cells, through the overexpression of LN-5 γ2, thereby resulting in an unfavorable clinical outcome in patients with tumors that show gene amplification and overexpression of EGFR.…”

Section: Discussionmentioning

confidence: 99%

Correlation between Laminin-5 γ2 Chain Expression and Epidermal Growth Factor Receptor Expression and Its Clinicopathological Significance in Squamous Cell Carcinoma of the Tongue

Katoh

Nakanishi²,

Akimoto³

et al. 2002

Oncology

View full text Add to dashboard Cite

Recent investigations have revealed that growth factors may influence the invasive activity of tumor cells. Expression of laminin-5 γ2 chain (LN-5 γ2) and epidermal growth factor receptor (EGFR) in squamous cell carcinomas of the tongue in 104 patients with stage II, III, and IVA, B (excluding the cases with distant metastasis) was examined immunohistochemically to determine the correlation between the two molecules and the associations with the clinicopathological features of each tumor. LN-5 γ2 expression was clearly demonstrated in the cytoplasm and EGFR in the cell membranes of cancer cells. A significant increase in positivity for LN-5 γ2 was observed in tumors showing poor differentiation (p < 0.001), infiltrative growth (p < 0.001), and deep invasion (p = 0.038). In a multivariate analysis, increased positivity for LN-5 γ2 was an independent predictor of an unfavorable outcome (p < 0.001). A significant increase in positivity for EGFR was observed in tumors showing infiltrative growth (p = 0.032) and poor prognosis (p = 0.008). The LN-5 γ2 expression was correlated significantly with EGFR expression (p < 0.001). Patients with tumor positivity for both molecules showed the worst prognosis (p < 0.001). LN-5 γ2 overexpression and EGFR overexpression is evident in tumors showing infiltrative growth, suggesting that EGFR may influence the invasive activity of tumor cells through overexpression of LN-5 γ2.

show abstract

“…After gelling was completed (45 minutes at 37jC), complete medium (2 mL) was added to the lower well and 1 Â 10 5 cells in complete medium were added to upper well. Following an additional 24-hour incubation at 37jC, epidermal growth factor (EGF) was added to the lower compartment of selected Transwell chambers at a final concentration of 10 ng/mL (48,49). The cells were grown on top of collagen gels for 12 days and medium was exchanged every 2 to 3 days.…”

Section: Methodsmentioning

confidence: 99%

Expression of Membrane Type 1 Matrix Metalloproteinase Is Associated with Cervical Carcinoma Progression and Invasion

Zhai¹,

Hotary²,

Nan

et al. 2005

Cancer Research

101

View full text Add to dashboard Cite

Membrane type 1 matrix metalloproteinase (MT1-MMP) is frequently expressed by cancer cells and is believed to play an important role in cancer cell invasion and metastasis. However, little is known about the role of MT1-MMP in mediating invasiveness of cervical cancer cells. In this study, we examined MT1-MMP expression in 58 primary human cervical tissue specimens, including normal cervix, low-grade squamous intraepithelial lesions (LSIL), high-grade SILs (HSIL), and invasive carcinomas. We also evaluated MT1-MMP, MMP-2, and tissue inhibitor of metalloproteinase-2 expression in several cervical cancer-derived cell lines, human papillomavirus (HPV)-immortalized keratinocytes, and keratinocytes derived from a LSIL. Using in situ hybridization techniques to study the cervical tissue specimens, we found that MT1-MMP expression increases with cervical tumor progression (Spearman correlation coefficient = 0.66; P < 0.0001, exact test). Specifically, MT1-MMP expression is very low or absent in normal cervix and LSILs, is readily detectable in HSILs, and is very strongly expressed in nearly all invasive carcinomas. Most but not all cervical cancerderived cell lines also expressed significant levels of MT1-MMP and MMP-2. Constitutive expression of exogenous MT1-MMP in cervical carcinoma-derived cells and HPVimmortalized keratinocytes with low endogenous levels of MT1-MMP induced invasiveness in collagen I, but this effect was not observed in LSIL-derived keratinocytes. Our results show that MT1-MMP is a key enzyme mediating cervical cancer progression. However, MT1-MMP alone is not always sufficient for inducing keratinocyte invasiveness at least in the collagen I invasion assay used in this study. Further studies of gene expression in preinvasive and invasive cervical cancers should assist with identification of additional critical factors mediating cervical cancer progression. (Cancer Res 2005; 65(15): 6543-50)

show abstract

Effects of EGF and TGF-α on Invasion and Proteinase Expression of Uterine Cervical Adenocarcinoma OMC-4 Cells

Cited by 21 publications

References 23 publications

Differentiated thyroid cancer cell invasion is regulated through epidermal growth factor receptor-dependent activation of matrix metalloproteinase (MMP)-2/gelatinase A

Differentiated thyroid cancer cell invasion is regulated through epidermal growth factor receptor-dependent activation of matrix metalloproteinase (MMP)-2/gelatinase A

Correlation between Laminin-5 γ2 Chain Expression and Epidermal Growth Factor Receptor Expression and Its Clinicopathological Significance in Squamous Cell Carcinoma of the Tongue

Expression of Membrane Type 1 Matrix Metalloproteinase Is Associated with Cervical Carcinoma Progression and Invasion

Contact Info

Product

Resources

About