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EGF/TGFβ1 co-stimulation of oral squamous cell carcinoma cells causes an epithelial-mesenchymal transition cell phenotype expressing laminin 332.
J Oral Pathol Med. 2011 Jan; 40(1):46-54.JO

Abstract

Epithelial-mesenchymal transition (EMT) is suggested to be crucial for the development of an invasive and metastatic carcinoma cell phenotype. Therefore, the definition of this phenotype is of great clinical interest. We recently evidenced vimentin positive cells in oral squamous cell carcinoma (OSCC) invasive front expressing laminin γ2 chain mRNA implicating an EMT origin of these cells. To further elucidate the nature of these cells, we have investigated the relation between EMT criteria and laminin-332 expression in a cell culture model of transforming growth factor beta-1 (TGFβ1)/epithelial growth factor (EGF) long time co-stimulation. We demonstrate that in contrast to TGFβ1 or EGF alone, co-stimulation induces phenotype transition in OSCC cells which fulfils the criteria of EMT in terms of vimentin up-regulation and E-cadherin down-regulation on protein level as well as cell scattering. Furthermore, cells displayed a strongly enhanced invasiveness and adhesion to type I-IV collagens. Phenotype transition is accompanied by an enhanced expression of laminin-332, especially of its γ2 chain. We further analyse the expression of extracellular matrix related genes by RT-PCR profiling. With respect to strongly enhanced proteins, data confirm the EMT phenotype of co-stimulated OSCC cells and expression of laminin-332. Furthermore, alpha catenin, collagen type 16, the integrin α7 and β1 chains, and MMP11 are suggested as candidates with potential role in EMT in OSCC. In summary we are able to show that EMT in OSCC is mediated by multiple growth factors and is accompanied by laminin γ2 chain up-regulation evidencing the existence of an intermediate Vim(+) /Ln332(+) EMT phenotype as seen in situ.

Authors+Show Affiliations

Institute of Pathology, University Hospital Jena, Jena, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20819124

Citation

Richter, Petra, et al. "EGF/TGFβ1 Co-stimulation of Oral Squamous Cell Carcinoma Cells Causes an Epithelial-mesenchymal Transition Cell Phenotype Expressing Laminin 332." Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology, vol. 40, no. 1, 2011, pp. 46-54.
Richter P, Umbreit C, Franz M, et al. EGF/TGFβ1 co-stimulation of oral squamous cell carcinoma cells causes an epithelial-mesenchymal transition cell phenotype expressing laminin 332. J Oral Pathol Med. 2011;40(1):46-54.
Richter, P., Umbreit, C., Franz, M., Berndt, A., Grimm, S., Uecker, A., Böhmer, F. D., Kosmehl, H., & Berndt, A. (2011). EGF/TGFβ1 co-stimulation of oral squamous cell carcinoma cells causes an epithelial-mesenchymal transition cell phenotype expressing laminin 332. Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology, 40(1), 46-54. https://doi.org/10.1111/j.1600-0714.2010.00936.x
Richter P, et al. EGF/TGFβ1 Co-stimulation of Oral Squamous Cell Carcinoma Cells Causes an Epithelial-mesenchymal Transition Cell Phenotype Expressing Laminin 332. J Oral Pathol Med. 2011;40(1):46-54. PubMed PMID: 20819124.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - EGF/TGFβ1 co-stimulation of oral squamous cell carcinoma cells causes an epithelial-mesenchymal transition cell phenotype expressing laminin 332. AU - Richter,Petra, AU - Umbreit,Claudia, AU - Franz,Marcus, AU - Berndt,Angela, AU - Grimm,Susanne, AU - Uecker,Andrea, AU - Böhmer,Frank D, AU - Kosmehl,Hartwig, AU - Berndt,Alexander, Y1 - 2010/08/31/ PY - 2010/9/8/entrez PY - 2010/9/8/pubmed PY - 2011/6/15/medline SP - 46 EP - 54 JF - Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology JO - J Oral Pathol Med VL - 40 IS - 1 N2 - Epithelial-mesenchymal transition (EMT) is suggested to be crucial for the development of an invasive and metastatic carcinoma cell phenotype. Therefore, the definition of this phenotype is of great clinical interest. We recently evidenced vimentin positive cells in oral squamous cell carcinoma (OSCC) invasive front expressing laminin γ2 chain mRNA implicating an EMT origin of these cells. To further elucidate the nature of these cells, we have investigated the relation between EMT criteria and laminin-332 expression in a cell culture model of transforming growth factor beta-1 (TGFβ1)/epithelial growth factor (EGF) long time co-stimulation. We demonstrate that in contrast to TGFβ1 or EGF alone, co-stimulation induces phenotype transition in OSCC cells which fulfils the criteria of EMT in terms of vimentin up-regulation and E-cadherin down-regulation on protein level as well as cell scattering. Furthermore, cells displayed a strongly enhanced invasiveness and adhesion to type I-IV collagens. Phenotype transition is accompanied by an enhanced expression of laminin-332, especially of its γ2 chain. We further analyse the expression of extracellular matrix related genes by RT-PCR profiling. With respect to strongly enhanced proteins, data confirm the EMT phenotype of co-stimulated OSCC cells and expression of laminin-332. Furthermore, alpha catenin, collagen type 16, the integrin α7 and β1 chains, and MMP11 are suggested as candidates with potential role in EMT in OSCC. In summary we are able to show that EMT in OSCC is mediated by multiple growth factors and is accompanied by laminin γ2 chain up-regulation evidencing the existence of an intermediate Vim(+) /Ln332(+) EMT phenotype as seen in situ. SN - 1600-0714 UR - https://www.unboundmedicine.com/medline/citation/20819124/EGF/TGFβ1_co_stimulation_of_oral_squamous_cell_carcinoma_cells_causes_an_epithelial_mesenchymal_transition_cell_phenotype_expressing_laminin_332_ L2 - https://doi.org/10.1111/j.1600-0714.2010.00936.x DB - PRIME DP - Unbound Medicine ER -