Evidence for a role of FGF-2 and FGF receptors in the proliferation of non-small cell lung cancer cells

Berger, Walter; Setinek, Ulrike; Mohr, Thomas; Kindås‐Mügge, Ingela; Vetterlein, M.; Dekan, Gerhard; Eckersberger, F.; Caldas, Carlos; Micksche, M.

doi:10.1002/(sici)1097-0215(19991029)83:3<415::aid-ijc19>3.0.co;2-y

Cited by 96 publications

(83 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alternatively, cell culture media were removed after drug exposure and 3 H-thymidine incorporation measured as described. 15 Cell cycle analysis was done after incubation of cells in the respective drug solutions and propidium iodide staining by flow cytometry (FACS) using standard protocols (FACS Calibur, Becton Dickinson). For determination of cell cycle distribution, Cell Quest software was used.…”

Section: Cell Culturesmentioning

confidence: 99%

Anticancer effects of zoledronic acid against human osteosarcoma cells

Kubista

Trieb

Sevelda

et al. 2006

Journal Orthopaedic Research

View full text Add to dashboard Cite

Based on neoadjuvant chemotherapy, the prognosis of osteosarcoma patients has improved dramatically. However, due to therapy resistance in patient subgroups, the development of new treatment strategies is still of utmost importance. The aim of our study was to test the effects of the nitrogen-containing bisphosphonate zoledronic acid (ZOL) on osteosarcoma cell lines (N ¼ 9). Exposure to ZOL at low micromolar concentrations induced a dose-and time-dependent block of DNA synthesis and cell cycle progression followed by microfilament breakdown and apoptosis induction. The ZOL-induced cell cycle accumulation in S phase was accompanied by significant changes in the expression of cyclins and cyclin-dependent kinase inhibitors with a prominent loss of cyclin E and D1. ZOL not only inhibited growth but also migration of osteosarcoma cells. The mevalonate pathway intermediary geranyl-geraniol (GGOH) but not farnesol (FOH) significantly inhibited the anticancer effects of ZOL against osteosarcoma cells. Correspondingly, ZOL sensitivity correlated with the blockade of protein geranylgeranylation indicated by unprenylated Rap1. Overexpression of even high levels of P-glycoprotein, as frequently present in therapy-resistant osteosarcomas, did not impair the anticancer activity of ZOL. Summarizing, our data suggest that ZOL, which selectively accumulates in the bone, represents a promising agent to improve osteosarcoma therapy. ß

show abstract

Section: Cell Culturesmentioning

confidence: 99%

Anticancer effects of zoledronic acid against human osteosarcoma cells

Kubista

Trieb

Sevelda

et al. 2006

Journal Orthopaedic Research

View full text Add to dashboard Cite

show abstract

“…Recently, autocrine signaling of fibroblast growth factors (FGF) and their receptors (FGFR) has been shown in NSCLC cell lines (17,18) with diverse cellular functions including proliferation, differentiation, and motility. They are also reported to be implicated in tumorigenesis as candidate "driver" oncogenes (19,20).…”

Section: Introductionmentioning

confidence: 99%

“…Numerous in vitro studies revealed frequent coexpression of specific FGFs as well as FGFR1 and FGFR2 (17,18,21), and several independent studies showed frequent coexpression of FGF2, FGFR1, and FGFR2 in primary NSCLC specimens (22)(23)(24). Importantly, inhibition of FGFR signaling via dominant-negative FGFR1 (21), FGF2 neutralizing antibodies (17), FGFR-TKI (18), or antisense RNA (18,25) blocked proliferation of tumor growth in NSCLC. These studies suggest that the FGF-FGFR autocrine growth pathway could be an important mechanism for intrinsic resistance to EGFR-TKI in NSCLC cell lines with wild-type EGFR (18).…”

Section: Introductionmentioning

confidence: 99%

Activation of the FGF2-FGFR1 Autocrine Pathway: A Novel Mechanism of Acquired Resistance to Gefitinib in NSCLC

Terai

Soejima

Yasuda

et al. 2013

Molecular Cancer Research

172

150

View full text Add to dashboard Cite

Patients with non-small cell lung cancer (NSCLC) that harbors epidermal growth factor receptor (EGFR) mutations initially respond to EGFR-tyrosine kinase inhibitors (TKI) but eventually experience relapse. Acquired resistance to EGFR-TKIs is strongly associated with patient mortality. Thus, elucidation of the mechanism of acquired resistance to EGFR-TKIs is of great importance. In this study, gefitinib-resistant cell line models were established by long-term exposure to gefitinib using the gefitinib-sensitive lung cancer cell lines, PC9 and HCC827. Expression analyses indicated that both FGFR1 and FGF2 were increased in PC9 gefitinib-resistant (PC9 GR) cells as compared with PC9 naïve (PC9 na) cells. Importantly, proliferation of gefitinib-resistant cells was dependent on the FGF2 -FGFR1 pathway. Mechanistically, inhibition of either FGF2 or FGFR1 by siRNA or FGFR inhibitor (PD173074) restored gefitinib sensitivity in PC9 GR cells. These data suggest that FGF2 -FGFR1 activation through an autocrine loop is a novel mechanism of acquired resistance to EGFR-TKIs. Mol Cancer Res; 11(7); 759-67. Ó2013 AACR.

show abstract

“…In addition many other tumor types express FGF-2/FGF-R at high levels (Berger et al, 1999;Sumitomo et al, 1999;Tamiya et al, 1998;Ueki et al, 1995;Xerri et al, 1996;Yoshimura et al, 1998).…”

mentioning

confidence: 99%

“…The selective effects of FGF-2 and VEGF on endothelial cells have been described to regulate cell proliferation (Goto et al, 1993), integrin expression and function (Senger et al, 1996), metalloproteinase activators (Mandriota and Pepper, 1997;Pepper et al, 1991Pepper et al, , 1998, matrix-dependent adhesion and migration (Senger et al, 1996), cell permeability and cell-cell junction alterations (Dellian et al, 1996;Hippenstiel et al, 1998), and morphogenic differentiation and vascular lumen formation (Pepper et al, 1992). FGF-2 is a growth factor that activates a proliferative response in many cell types in addition to endothelial cells, including stromal and tissue fibroblasts (Berger et al, 1999;Ittman and Mansukhani, 1997;Sumitomo et al, 1999;Yoshimura et al, 1998). The role of FGF-2 in promoting a stromal response in relation to tumor angiogenesis has not been addressed to date.…”

mentioning

confidence: 99%