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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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Related in: MedlinePlus

Kaplan–Meier survival curves for patients with high and low FGFR2 expression. Patients with low FGFR2 expression had a significantly longer overall survival time compared to those with high FGFR2 expression (P<0.05 by log-rank test).
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fig2: Kaplan–Meier survival curves for patients with high and low FGFR2 expression. Patients with low FGFR2 expression had a significantly longer overall survival time compared to those with high FGFR2 expression (P<0.05 by log-rank test).

Mentions: Next, we examined whether strong expression of FGFR2 in cancer cells correlated with patient prognosis. The 76 patients were divided into two groups according to the expression level of FGFR2 in cancer cells (the high and low expression groups in Table 1). The expression level of FGFR2 was not correlated with clinicopathological factors such as sex, age and pathological stage (Table 1). There were no statistical differences in the resection status of both groups. Also, the ratios of patients who received adjuvant chemotherapy (using gemcitabine) were similar in both groups, indicating that patients in both groups were treated with similar therapeutic approaches after surgery (Table 1). Interestingly, Kaplan–Meier analysis showed that patients with high FGFR2 expression had a significantly shorter overall survival time compared to those with low expression levels (Figure 2) (P=0.047 by log-rank test). Moreover, patients with high FGFR2 expression had significantly more nodal invasion, a larger tumour size, and a worse UICC Stage (Table 2; P=0.0263, P=0.0469, and P=0.022, respectively, by χ2-test). There was no significant correlation between survival time and the presence of FGF10 in stromal cells in cancer tissue (data not shown).


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)

Kaplan–Meier survival curves for patients with high and low FGFR2 expression. Patients with low FGFR2 expression had a significantly longer overall survival time compared to those with high FGFR2 expression (P<0.05 by log-rank test).
© Copyright Policy
Related In: Results  -  Collection

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

fig2: Kaplan–Meier survival curves for patients with high and low FGFR2 expression. Patients with low FGFR2 expression had a significantly longer overall survival time compared to those with high FGFR2 expression (P<0.05 by log-rank test).
Mentions: Next, we examined whether strong expression of FGFR2 in cancer cells correlated with patient prognosis. The 76 patients were divided into two groups according to the expression level of FGFR2 in cancer cells (the high and low expression groups in Table 1). The expression level of FGFR2 was not correlated with clinicopathological factors such as sex, age and pathological stage (Table 1). There were no statistical differences in the resection status of both groups. Also, the ratios of patients who received adjuvant chemotherapy (using gemcitabine) were similar in both groups, indicating that patients in both groups were treated with similar therapeutic approaches after surgery (Table 1). Interestingly, Kaplan–Meier analysis showed that patients with high FGFR2 expression had a significantly shorter overall survival time compared to those with low expression levels (Figure 2) (P=0.047 by log-rank test). Moreover, patients with high FGFR2 expression had significantly more nodal invasion, a larger tumour size, and a worse UICC Stage (Table 2; P=0.0263, P=0.0469, and P=0.022, respectively, by χ2-test). There was no significant correlation between survival time and the presence of FGF10 in stromal cells in cancer tissue (data not shown).

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