FGF18 in colorectal tumour cells: Autocrine and paracrine effects

Gudrun Sonvilla, Sigrid Allerstorfer, Stefan Stättner, J. Karner, Martin Klimpfinger, Hendrik Fischer, Bettina Grasl-Kraupp, Klaus Holzmann, Walter Berger, Friedrich Wrba, Brigitte Marian, Michael Grusch

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Abstract

Fibroblast growth factors (FGFs) and their high-affinity receptors contribute to the autocrine growth stimulation in several human malignancies. Here, we describe that FGF18 expression is up-regulated in 34/38 colorectal tumours and is progressively enhanced during colon carcinogenesis reaching very high levels in carcinoma. Moreover, our data suggest that FGF18 affects both tumour cells and tumour microenvironment in a pro-tumorigenic and pro-metastatic way. Addition of recombinant FGF18 to the culture media of slowly growing colorectal tumour cell lines LT97 and Caco-2 stimulated proliferation. Phosphorylation of externally regulated kinase 1/2 and S6 was increased already 5 min after growth factor addition. SW480 cells, endogenously producing large amounts of FGF18, were not affected in this setting, but recombinant FGF18 supported tumour cell survival under conditions of serum starvation. Down-modulation of endogenous FGF18 production by small interference RNA (siRNA) significantly reduced clonogenicity of SW480 cells and restored sensitivity to exogenous FGF18. With respect to the tumour microenvironment, both recombinant and tumour-derived FGF18 stimulated growth of colon-associated fibroblasts at 0.1 ng/ml and migration at 10 ng/ml. In addition, recombinant FGF18 (10 ng/ml) induced tube formation in human umbilical vein endothelial cells. siRNA knock down demonstrated that tube-forming activity of colon cancer cell supernatants depended to a large part on tumour cell-derived FGF18. In summary, this study demonstrates that FGF18 is almost generally over-expressed in colon cancer and exerts pro-tumorigenic effects both in the epithelial and the stromal compartments by stimulating growth and survival of tumour cells, migration of fibroblasts and neovascularization. Together, these data strongly support an oncogenic role of FGF18 in colorectal cancer.

Original languageEnglish
Pages (from-to)15-24
Number of pages10
JournalCarcinogenesis
Volume29
Issue number1
DOIs
Publication statusPublished - Jan 2008

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Colorectal Neoplasms
Neoplasms
Tumor Microenvironment
RNA Interference
Colonic Neoplasms
Colon
Growth
Fibroblasts
Cellular Microenvironment
S 6
Fibroblast Growth Factors
Human Umbilical Vein Endothelial Cells
Starvation
Tumor Cell Line
Cell Movement
Culture Media
Cell Survival
Intercellular Signaling Peptides and Proteins
Carcinogenesis
Phosphotransferases

ASJC Scopus subject areas

  • Cancer Research

Cite this

Sonvilla, G., Allerstorfer, S., Stättner, S., Karner, J., Klimpfinger, M., Fischer, H., ... Grusch, M. (2008). FGF18 in colorectal tumour cells: Autocrine and paracrine effects. Carcinogenesis, 29(1), 15-24. https://doi.org/10.1093/carcin/bgm202

FGF18 in colorectal tumour cells : Autocrine and paracrine effects. / Sonvilla, Gudrun; Allerstorfer, Sigrid; Stättner, Stefan; Karner, J.; Klimpfinger, Martin; Fischer, Hendrik; Grasl-Kraupp, Bettina; Holzmann, Klaus; Berger, Walter; Wrba, Friedrich; Marian, Brigitte; Grusch, Michael.

In: Carcinogenesis, Vol. 29, No. 1, 01.2008, p. 15-24.

Research output: Contribution to journalArticle

Sonvilla, G, Allerstorfer, S, Stättner, S, Karner, J, Klimpfinger, M, Fischer, H, Grasl-Kraupp, B, Holzmann, K, Berger, W, Wrba, F, Marian, B & Grusch, M 2008, 'FGF18 in colorectal tumour cells: Autocrine and paracrine effects', Carcinogenesis, vol. 29, no. 1, pp. 15-24. https://doi.org/10.1093/carcin/bgm202
Sonvilla G, Allerstorfer S, Stättner S, Karner J, Klimpfinger M, Fischer H et al. FGF18 in colorectal tumour cells: Autocrine and paracrine effects. Carcinogenesis. 2008 Jan;29(1):15-24. https://doi.org/10.1093/carcin/bgm202
Sonvilla, Gudrun ; Allerstorfer, Sigrid ; Stättner, Stefan ; Karner, J. ; Klimpfinger, Martin ; Fischer, Hendrik ; Grasl-Kraupp, Bettina ; Holzmann, Klaus ; Berger, Walter ; Wrba, Friedrich ; Marian, Brigitte ; Grusch, Michael. / FGF18 in colorectal tumour cells : Autocrine and paracrine effects. In: Carcinogenesis. 2008 ; Vol. 29, No. 1. pp. 15-24.
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