Expression of fibroblast growth factor and FGF-receptor family genes in human myeloma cells, including lines possessing t(4;14)(q16.3;q32. 3) and FGFR3 translocation.

Otsuki, Takemi; Yata, Kenichiro; Sakaguchi, Haruko; Kurebayashi, Junichi; Nakazawa, Naozo; Yawata, Yoshihito; Ueki, Ayako

doi:10.3892/ijo.15.6.1205

Cited by 37 publications

(42 citation statements)

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“…17 Both VEGF and bFGF stimulate angiogenesis and elevated levels in the plasma of MM patients have been reported. 18,20 MIP-1a has been shown to induce proliferation and migration in MM cell lines and to activate human osteoclasts. Elevated levels have been found in the bone marrow of MM patients, suggesting that this cytokine could be involved in the development of osteolytic lesions in MM.…”

Section: Discussionmentioning

confidence: 99%

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PI3-K/AKT/FKHR and MAPK signaling cascades are redundantly stimulated by a variety of cytokines and contribute independently to proliferation and survival of multiple myeloma cells

et al. 2004

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Section: Discussionmentioning

confidence: 99%

“…In addition, it has been demonstrated that corresponding receptors of these cytokines are expressed by MM cells and therefore these cytokines can play a role in MM. [17][18][19][20][21][22][23][24][25][26][27][28] Nevertheless, with exception of IL-6, the precise role of these cytokines in MM is still unclear.…”

Section: Introductionmentioning

confidence: 99%

PI3-K/AKT/FKHR and MAPK signaling cascades are redundantly stimulated by a variety of cytokines and contribute independently to proliferation and survival of multiple myeloma cells

et al. 2004

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“…For example, four of five cell lines harboring the t(4;14) translocation of FGFR3/MMSET were determined to be sensitive to lovastatin-induced apoptosis. Furthermore, Otsuki et al (2,57) assayed a panel of MM cell lines characterized to express FGFR3 and has shown them to be largely sensitive to apoptosis induced by simvastatin. Although these results suggest an association between t(4;14) and sensitivity to statin-induced apoptosis, the translocation alone was not significantly associated with sensitivity (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Determinants of sensitivity to lovastatin-induced apoptosis in multiple myeloma

Wong

Clendening

Martirosyan

et al. 2007

Molecular Cancer Therapeutics

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Statins, commonly used to treat hypercholesterolemia, have been shown to trigger tumor-specific apoptosis in certain cancers, including multiple myeloma (MM), a plasma cell malignancy with poor prognosis. In this article, we show that of a panel of 17 genetically distinct MM cell lines, half were sensitive to statin-induced apoptosis and, despite pharmacodynamic evidence of drug uptake and activity, the remainder were insensitive. Sensitive cells were rescued from lovastatin-induced apoptosis by mevalonate, geranylgeranyl PPi, and partially by farnesyl PPi, highlighting the importance of isoprenylation. Expression profiling revealed that Rho GTPase mRNAs were differentially expressed upon lovastatin exposure in sensitive cells, yet ectopic expression of constitutively active Rho or Ras proteins was insufficient to alter sensitivity to lovastatin-induced apoptosis. This suggests that sensitivity involves more than one isoprenylated protein and that statins trigger apoptosis by blocking many signaling cascades, directly or indirectly deregulated by the oncogenic lesions of the tumor cell. Indeed, clustering on the basis of genetic abnormalities was shown to be significantly associated with sensitivity (P = 0.003). These results suggest that statins may be a useful molecular targeted therapy in the treatment of a subset of MM. [Mol Cancer Ther 2007;6(6):1886 -97]

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“…This translocation is intergenic, with the breakpoints occurring ∼70 kb upstream of FGFR3, and brings FGFR3 under the control of the highly active IGH promoter. The ultimate effect of this translocation is the overexpression of FGFR3 out of context, that may result in aberrant hypersensitivity to ligands [69] or to ligand-independent signalling. The t(4;14) translocation is associated with poor prognosis in MM, FGFR3 representing an attractive therapeutic target for this tumor.…”

Section: Chromosomal Translocationsmentioning

confidence: 99%

Blocking the FGF/FGFR system as a ⿿two-compartment⿿ antiangiogenic/antitumor approach in cancer therapy

Giacomini

Chiodelli

Matarazzo

et al. 2016

Pharmacological Research

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a b s t r a c tFibroblast growth factors (FGFs) are a family of pleiotropic factors produced by stromal and parenchymal tumor cells. Even though FGFs have been firstly characterized as angiogenic factors, they exert autocrine and paracrine functions not only on endothelial cells but also on tumor cells and other stromal components. Thus, the FGF/FGF receptor (FGFR) pathway may represent a key player in tumor growth by regulating the complex cross-talk between stromal and tumor compartments.The ligand dependent or independent activation of the FGF/FGFR system by gene upregulation, oncogenic mutation or amplification occurs in a variety of human tumors and is implicated in various key steps of tumor growth and progression. In addition, FGF/FGFR activation has been described as a mechanism of tumor escape in response to antiangiogenic/anti-VEGF therapies.Experimental and clinical evidences provide a compelling biologic rationale for the development of anti-FGF/FGFR targeting agents in cancer therapy. However, the development of drugs specifically targeting the FGF/FGFR pathway proved to be difficult, also due to the high redundancy and pleiotropic effects of FGF and FGFR family members. On the other hand, the possibility to develop "two-compartment" targeting agents endowed with both antiangiogenic and antitumor activities remains promising.Here we will review the preclinical and clinical approaches and potential therapeutics currently available to block the FGF/FGFR system in human cancer.

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Expression of fibroblast growth factor and FGF-receptor family genes in human myeloma cells, including lines possessing t(4;14)(q16.3;q32. 3) and FGFR3 translocation.

Cited by 37 publications

References 0 publications

PI3-K/AKT/FKHR and MAPK signaling cascades are redundantly stimulated by a variety of cytokines and contribute independently to proliferation and survival of multiple myeloma cells

PI3-K/AKT/FKHR and MAPK signaling cascades are redundantly stimulated by a variety of cytokines and contribute independently to proliferation and survival of multiple myeloma cells

Determinants of sensitivity to lovastatin-induced apoptosis in multiple myeloma

Blocking the FGF/FGFR system as a ⿿two-compartment⿿ antiangiogenic/antitumor approach in cancer therapy

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