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FGF10/FGFR2 signal induces cell migration and invasion in pancreatic cancer.

Nomura S, Yoshitomi H, Takano S, Shida T, Kobayashi S, Ohtsuka M, Kimura F, Shimizu H, Yoshidome H, Kato A, Miyazaki M - Br. J. Cancer (2008)

Bottom Line: Fibroblast growth factor 10 also induced expression of mRNA for membrane type 1-matrix metalloproteinase (MT1-MMP) and transforming growth factor (TGF)-beta1, and increased secretion of TGF-beta1 protein from these cell lines.These data indicate that stromal FGF10 induces migration and invasion in pancreatic cancer cells through interaction with FGFR2, resulting in a poor prognosis.This suggests that FGF10/FGFR2 signalling is a promising target for new molecular therapy against pancreatic cancer.

View Article: PubMed Central - PubMed

Affiliation: The Department of General Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba city, Chiba 260-8670, Japan.

ABSTRACT
Pancreatic cancer has one of the highest mortalities among all malignancies and there is an urgent need for new therapy. This might be achieved by resolving the detailed biological mechanism, and in this study we examined how pancreatic cancer cells develop aggressive properties by focusing on signalling through the fibroblast growth factor (FGF)10 and FGF receptor (FGFR)2, which play important roles in pancreatic organogenesis. Immunostaining of pancreatic cancer tissues showed that FGFR2 was expressed in cancer cells, whereas FGF10 was expressed in stromal cells surrounding the cancer cells. Patients with high FGFR2 expression in cancer cells had a shorter survival time compared to those with low FGFR2 expression. Fibroblast growth factor 10 induced cell migration and invasion of CFPAC-1 and AsPC-1 pancreatic cancer cells through interaction with FGFR2-IIIb, a specific isoform of FGFR2. Fibroblast growth factor 10 also induced expression of mRNA for membrane type 1-matrix metalloproteinase (MT1-MMP) and transforming growth factor (TGF)-beta1, and increased secretion of TGF-beta1 protein from these cell lines. These data indicate that stromal FGF10 induces migration and invasion in pancreatic cancer cells through interaction with FGFR2, resulting in a poor prognosis. This suggests that FGF10/FGFR2 signalling is a promising target for new molecular therapy against pancreatic cancer.

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Expression patterns of FGFR2 and FGF10 in normal pancreas and pancreatic cancer. The magnification is shown in the right bottom corner of each figure. (A and B) Immunostaining of FGFR2 (A) and FGF10 (B) in normal pancreas, showing that FGFR2 is expressed weakly in ductal cells (A, arrow) and acinar cells (A, arrow head), and that no obvious FGF10 staining is found in normal pancreatic tissue, including ductal cells (B, arrows). (C and D) Immunostaining of FGFR2 (C) and FGF10 (D) in pancreatic cancer tissues, showing that FGFR2 is expressed in cancer cells (C), whereas FGF10 is expressed in scattered cells in the stroma surrounding cancer cells (D, arrows). (E and F) Immunostaining of FGFR2 in pancreatic cancer cells. (E) Representative result from the FGFR2 high expression group, indicating higher FGFR2 expression in cancer cells (arrows) compared with islets (arrow head). (F) Representative result from the FGFR2 low expression group, showing lower FGFR2 expression in cancer cells (arrows) compared with islet (arrow heads). (G and H) Immunostaining of FGF10 (G) and CD3 (H), marker for T cell. Fibroblast growth factor 10 and CD3 are both expressed in scattered cells with similar cell shape in the stroma surrounding cancer cells (arrows).
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fig1: Expression patterns of FGFR2 and FGF10 in normal pancreas and pancreatic cancer. The magnification is shown in the right bottom corner of each figure. (A and B) Immunostaining of FGFR2 (A) and FGF10 (B) in normal pancreas, showing that FGFR2 is expressed weakly in ductal cells (A, arrow) and acinar cells (A, arrow head), and that no obvious FGF10 staining is found in normal pancreatic tissue, including ductal cells (B, arrows). (C and D) Immunostaining of FGFR2 (C) and FGF10 (D) in pancreatic cancer tissues, showing that FGFR2 is expressed in cancer cells (C), whereas FGF10 is expressed in scattered cells in the stroma surrounding cancer cells (D, arrows). (E and F) Immunostaining of FGFR2 in pancreatic cancer cells. (E) Representative result from the FGFR2 high expression group, indicating higher FGFR2 expression in cancer cells (arrows) compared with islets (arrow head). (F) Representative result from the FGFR2 low expression group, showing lower FGFR2 expression in cancer cells (arrows) compared with islet (arrow heads). (G and H) Immunostaining of FGF10 (G) and CD3 (H), marker for T cell. Fibroblast growth factor 10 and CD3 are both expressed in scattered cells with similar cell shape in the stroma surrounding cancer cells (arrows).

Mentions: To examine the expression pattern of FGFR2 and FGF10 in pancreatic cancer tissues, we performed immunohistochemical staining of 76 tissue samples of invasive pancreatic ductal carcinoma and of normal pancreatic tissues. FGF receptor-2 immunoreactivity was weak to moderate in pancreatic ductal cells in normal tissues (Figure 1A; arrow) and acinar cells (Figure 1A; arrowhead), as well as in islet cells (data not shown), as described previously (Ishiwata et al, 2002). On the other hand, immunostaining of FGF10 did not occur in normal pancreatic tissue, as also described previously (Ishiwata et al, 2002) (Figure 1B).


FGF10/FGFR2 signal induces cell migration and invasion in pancreatic cancer.

Nomura S, Yoshitomi H, Takano S, Shida T, Kobayashi S, Ohtsuka M, Kimura F, Shimizu H, Yoshidome H, Kato A, Miyazaki M - Br. J. Cancer (2008)

Expression patterns of FGFR2 and FGF10 in normal pancreas and pancreatic cancer. The magnification is shown in the right bottom corner of each figure. (A and B) Immunostaining of FGFR2 (A) and FGF10 (B) in normal pancreas, showing that FGFR2 is expressed weakly in ductal cells (A, arrow) and acinar cells (A, arrow head), and that no obvious FGF10 staining is found in normal pancreatic tissue, including ductal cells (B, arrows). (C and D) Immunostaining of FGFR2 (C) and FGF10 (D) in pancreatic cancer tissues, showing that FGFR2 is expressed in cancer cells (C), whereas FGF10 is expressed in scattered cells in the stroma surrounding cancer cells (D, arrows). (E and F) Immunostaining of FGFR2 in pancreatic cancer cells. (E) Representative result from the FGFR2 high expression group, indicating higher FGFR2 expression in cancer cells (arrows) compared with islets (arrow head). (F) Representative result from the FGFR2 low expression group, showing lower FGFR2 expression in cancer cells (arrows) compared with islet (arrow heads). (G and H) Immunostaining of FGF10 (G) and CD3 (H), marker for T cell. Fibroblast growth factor 10 and CD3 are both expressed in scattered cells with similar cell shape in the stroma surrounding cancer cells (arrows).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2480967&req=5

fig1: Expression patterns of FGFR2 and FGF10 in normal pancreas and pancreatic cancer. The magnification is shown in the right bottom corner of each figure. (A and B) Immunostaining of FGFR2 (A) and FGF10 (B) in normal pancreas, showing that FGFR2 is expressed weakly in ductal cells (A, arrow) and acinar cells (A, arrow head), and that no obvious FGF10 staining is found in normal pancreatic tissue, including ductal cells (B, arrows). (C and D) Immunostaining of FGFR2 (C) and FGF10 (D) in pancreatic cancer tissues, showing that FGFR2 is expressed in cancer cells (C), whereas FGF10 is expressed in scattered cells in the stroma surrounding cancer cells (D, arrows). (E and F) Immunostaining of FGFR2 in pancreatic cancer cells. (E) Representative result from the FGFR2 high expression group, indicating higher FGFR2 expression in cancer cells (arrows) compared with islets (arrow head). (F) Representative result from the FGFR2 low expression group, showing lower FGFR2 expression in cancer cells (arrows) compared with islet (arrow heads). (G and H) Immunostaining of FGF10 (G) and CD3 (H), marker for T cell. Fibroblast growth factor 10 and CD3 are both expressed in scattered cells with similar cell shape in the stroma surrounding cancer cells (arrows).
Mentions: To examine the expression pattern of FGFR2 and FGF10 in pancreatic cancer tissues, we performed immunohistochemical staining of 76 tissue samples of invasive pancreatic ductal carcinoma and of normal pancreatic tissues. FGF receptor-2 immunoreactivity was weak to moderate in pancreatic ductal cells in normal tissues (Figure 1A; arrow) and acinar cells (Figure 1A; arrowhead), as well as in islet cells (data not shown), as described previously (Ishiwata et al, 2002). On the other hand, immunostaining of FGF10 did not occur in normal pancreatic tissue, as also described previously (Ishiwata et al, 2002) (Figure 1B).

Bottom Line: Fibroblast growth factor 10 also induced expression of mRNA for membrane type 1-matrix metalloproteinase (MT1-MMP) and transforming growth factor (TGF)-beta1, and increased secretion of TGF-beta1 protein from these cell lines.These data indicate that stromal FGF10 induces migration and invasion in pancreatic cancer cells through interaction with FGFR2, resulting in a poor prognosis.This suggests that FGF10/FGFR2 signalling is a promising target for new molecular therapy against pancreatic cancer.

View Article: PubMed Central - PubMed

Affiliation: The Department of General Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba city, Chiba 260-8670, Japan.

ABSTRACT
Pancreatic cancer has one of the highest mortalities among all malignancies and there is an urgent need for new therapy. This might be achieved by resolving the detailed biological mechanism, and in this study we examined how pancreatic cancer cells develop aggressive properties by focusing on signalling through the fibroblast growth factor (FGF)10 and FGF receptor (FGFR)2, which play important roles in pancreatic organogenesis. Immunostaining of pancreatic cancer tissues showed that FGFR2 was expressed in cancer cells, whereas FGF10 was expressed in stromal cells surrounding the cancer cells. Patients with high FGFR2 expression in cancer cells had a shorter survival time compared to those with low FGFR2 expression. Fibroblast growth factor 10 induced cell migration and invasion of CFPAC-1 and AsPC-1 pancreatic cancer cells through interaction with FGFR2-IIIb, a specific isoform of FGFR2. Fibroblast growth factor 10 also induced expression of mRNA for membrane type 1-matrix metalloproteinase (MT1-MMP) and transforming growth factor (TGF)-beta1, and increased secretion of TGF-beta1 protein from these cell lines. These data indicate that stromal FGF10 induces migration and invasion in pancreatic cancer cells through interaction with FGFR2, resulting in a poor prognosis. This suggests that FGF10/FGFR2 signalling is a promising target for new molecular therapy against pancreatic cancer.

Show MeSH
Related in: MedlinePlus