Fibroblast growth factors modulate intestinal epithelial cell growth and migration

Dignaß, Axel; Shoji, Takuhito; Podolsky, Daniel K.

doi:10.1016/0016-5085(94)90017-5

Cited by 256 publications

(166 citation statements)

References 27 publications

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“…It has been shown that stromal fibroblasts supply many of the angiogenetic factors to the microenvironment of the healing wound and cancer (Fukumura et al, 1998). As expected from the findings of our cell proliferation assays using conditioned media, we identified upregulated secreted factors and cytokines that have been shown to promote cancer cell growth and survival including PDGF (Westermark and Heldin, 1991), TGFB2 (Derynck et al, 2001), FGF1 (Dignass et al, 1994), IGF binding proteins (Miyakoshi et al, 2001), MCP1 (Youngs et al, 1997), IL-6 (Conze et al, 2001), osteoprotegrin (Holen et al, 2002), ICAM1 (Gho et al, 2001), follistatin and its homologue FLRG (Bartholin et al 2002). Growth factors (e.g.…”

Section: Discussionsupporting

confidence: 76%

Role of cancer-associated stromal fibroblasts in metastatic colon cancer to the liver and their expression profiles

et al. 2004

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The cancer microenvironment and interaction between cancer and stromal cells play critical roles in tumor development and progression. The molecular features of cancer stroma are less well understood than those of cancer cells. Cancer-associated stromal fibroblasts are the predominant component of stroma associated with colon cancer and its functions remain unclear. Fibroblast cell cultures were established from metastatic colon cancer in liver, liver away from the metastatic lesions, and skin from three patients with metastatic colorectal cancer. We generated expression profiles of cancer-associated fibroblasts using oligochip arrays and compared them to those of uninvolved fibroblasts. The conditioned media from the cancer-associated fibroblast cultures enhanced proliferation of colon cancer cell line HCT116 to a greater extent than cultures from uninvolved fibroblasts. In microarray expression analysis, cancer-associated fibroblasts clustered tightly into one group and skin fibroblasts into another. Approximately 170 of 22 000 genes were upregulated in cancer-associated fibroblasts (fold change42, Po0.05) as compared to skin fibroblasts, including many genes encoding cell adhesion molecules, growth factors, and COX2. By immunohistochemistry in-vivo, we confirmed COX2 and TGFB2 expression in cancer-associated fibroblasts in metastatic colon cancer. The distinct molecular expression profiles of cancerassociated fibroblasts in colon cancer metastasis support the notion that these fibroblasts form a favorable microenvironment for cancer cells.

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Section: Discussionsupporting

confidence: 76%

Role of cancer-associated stromal fibroblasts in metastatic colon cancer to the liver and their expression profiles

et al. 2004

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“…FGF1 is a pleiotropic growth factor known to regulate proliferation, migration, and differentiation of target cells, and it has been shown to promote intestinal epithelial cell migration. 17 A recent article has additionally shown that overexpression of FGFR correlates with liver metastasis in CRC, 18 and the splice form IIIc of FGFR3 has been suggested to have oncogenic effect on CRC cells. 19 Because both a block of FGFR and use of a neutralizing FGF1 antibody attenuated cancer cell migration in our assay, we speculate that FGF signaling might be one pathway responsible for the low clinical efficiency seen when using the FAP-inhibitor talabostat on metastatic CRC patients.…”

Section: Discussionmentioning

confidence: 99%

Colorectal Cancer Cells Activate Adjacent Fibroblasts Resulting in FGF1/FGFR3 Signaling and Increased Invasion

Henriksson

Edin

Dahlin

et al. 2011

The American Journal of Pathology

118

100

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Cancer-associated fibroblasts expressing fibroblast activation protein (FAP) have been implicated in the invasive behavior of colorectal cancer. In this study, we use FAP expression as a marker of fibroblast activation and analyze the effect of activated fibroblasts on colorectal cancer migration and invasion in experimental cell studies. We also investigated the expression pattern of FAP in cancer-associated fibroblasts during transformation from benign to malignant colorectal tumors. In immunohistochemical analyses, FAP was expressed in fibroblasts in all colorectal cancer samples examined, whereas all normal colon, hyperplastic polyps, or adenoma samples were negative. In in vitro studies, conditioned medium from colon cancer cells, but not adenoma cells, activated fibroblasts by inducing FAP expression. These activated fibroblasts increased the migration and invasion of colon cancer cells in Boyden chamber experiments and in a three-dimensional cell culture model. We identify fibroblast growth factor 1/fibroblast growth factor receptor 3 (FGF1/FGFR-3) signaling as mediators leading to the increased migration and invasion. Activated fibroblasts increase their expression of FGF1, and by adding a fibroblast growth factor receptor inhibitor, as well as an FGF1-neutralizing antibody, we reduced the migration of colon cancer cells. Our findings provide evidence of a possible molecular mechanism involved in the cross talk between cancer cells and fibroblasts leading to cancer cell invasion.

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“…In a human gastric adenocarcinoma cell line, hepatocyte growth factor and transforming growth factor-␤ (TGF-␤) have been shown to stimulate in vitro invasion; 45 in the intestinal epithelial cell line IEC-6, fibroblast growth factor and keratinocyte growth factor stimulated cell migration in an in vitro wound model. 46 The v-erbA oncogene coding for a truncated thyroid hormone receptor has been shown to cooperate with platelet-derived growth factor to increase in vitro invasion. 47 In other cell types a role for the EGFR has also been demonstrated; for example, Hölting et al 48 showed that in a follicular thyroid cancer cell line EGF or TGF-␣ stimulated invasion over unstimulated cells (p Ͻ 0.02).…”

Section: Discussionmentioning

confidence: 99%

Epidermal growth factor receptor mutation type iii transfected into a small cell lung cancer cell line is predominantly localized at the cell surface and enhances the malignant phenotype

Damstrup

Pedersen

Bastholm

et al. 2001

Intl Journal of Cancer

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In the present study we transfected the epidermal growth factor receptor (EGFR)-negative small cell lung cancer cell line, GLC3, with the type III EGFR mutation (EGFRvIII). The EGFRvIII protein could be detected by Western blot analysis as a 145-kDa protein, which by immunohistochemistry appeared to be localized at the cell surface. Ultrastructurally EGFRvIII was expressed mainly at the cell surface with clusters at cell-cell contacts. In the in vitro invasion assay, GLC3-EGFRvIII cells had a Ϸ5-fold increased invasion compared with uninduced GLC3-EGFRvIII, GLC3-Tet-On and the parental cell line. GLC3-Tet-On appeared uniform in size with adherence junctions at cell-cell contacts. In uninduced GLC3-EGFRvIII cells adherence junctions were also present but less distinct. In doxycycline-pretreated GLC3-EGFRvIII cells, adherence junctions were absent. We conclude that the expression of EGFRvIII results in a more malignant phenotype. This effect appears to involve the disruption of adherence junctions.

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Fibroblast growth factors modulate intestinal epithelial cell growth and migration

Cited by 256 publications

References 27 publications

Role of cancer-associated stromal fibroblasts in metastatic colon cancer to the liver and their expression profiles

Role of cancer-associated stromal fibroblasts in metastatic colon cancer to the liver and their expression profiles

Colorectal Cancer Cells Activate Adjacent Fibroblasts Resulting in FGF1/FGFR3 Signaling and Increased Invasion

Epidermal growth factor receptor mutation type iii transfected into a small cell lung cancer cell line is predominantly localized at the cell surface and enhances the malignant phenotype

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