Pleiotropic function of FGF‐4: Its role in development and stem cells

Kosaka, Nobuyoshi; Sanada, Hiromi; Terada, Masaaki; Ochiya, Takahiro

doi:10.1002/dvdy.21699

Cited by 47 publications

(34 citation statements)

References 132 publications

(144 reference statements)

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“…This may suggest that FGF4 may not be regulated through the Oct4-Sox2 complex but by another system or pathways that caused the upregulation of FGF4 at P20 of ASCs. In addition, FGF4 may also be a cancer marker as it was found to be upregulated in breast cancer via Oct3 activation [29,30]. However, in this study, we believe that the increase in FGF4 expression is due to the feedback mechanism of maintaining the self-renewal ability of ASCs at later passage when the growth kinetics of ASCs was slowing down.…”

Section: Discussioncontrasting

confidence: 67%

The changes of stemness biomarkers expression in human adipose‐derived stem cells during long‐term manipulation

Safwani

Makpol

Sathapan

et al. 2011

Biotech and App Biochem

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One of the advantages of human adipose-derived stem cells (ASCs) in regenerative medicine is that they can be harvested in abundance. However, the stemness biomarkers, which marked the safety and efficacy of ASCs in accordance with the good manufacturing practice guidelines, is not yet well established. This study was designed to investigate the effect of long-term culture on the stemness properties of ASCs using quantitative real-time polymerase chain reaction and flow cytometry. Results showed the growth rate of ASCs was at its peak when they reached P10 (population doubling; PD = 26) but started to decrease when they were expanded to P15 (PD = 36) and P20 (PD = 46). The ASCs can be culture expanded with minimal alteration in the stemness genes and cluster of differentiation (CD) markers expression up to P10. Expression level of Sox2, Nestin, and Nanog3 was significantly decreased at later passage. CD31, CD45, CD117, and human leukocyte antigen DR, DQ, and DP were lowly expressed at P5 and P10 but their expressions increased significantly at P15 or P20. The differentiation ability of ASCs (adipogenesis, osteogenesis, and neurogenesis) also decreased in long-term culture. Our findings suggested that P10 (PD = 26) should be the "cutoff point" for clinical usage because ASCs at passage 15 onward showed significant changes in the stemness genes, CD markers expression, and differentiation capability.

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Section: Discussioncontrasting

confidence: 67%

The changes of stemness biomarkers expression in human adipose‐derived stem cells during long‐term manipulation

Safwani

Makpol

Sathapan

et al. 2011

Biotech and App Biochem

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“…In response to CaSR stimulation, MDA-MB-231 breast cancer cells secrete GM-CSF, EGF, MDC, FGF-4 and IGFBP-2 via a mechanism that requires transactivation of EGFR and involves ERK, PI3K-AKT-mTOR and PKC signaling pathways. The identified cytokines and growth factors most likely exert an integrated effect on endothelial cells, as independent reports focusing on individual cytokines and growth factors have demonstrated their angiogenic potential [78][79][80][81][82][83][84][85][86]. Thus, our results suggest that the joint potential of multiple chemotactic and angiogenic mediators secreted in response to CaSR activation putatively contributes to the aggressiveness of breast cancer cells.…”

Section: Discussionmentioning

confidence: 67%

Chemotactic and proangiogenic role of calcium sensing receptor is linked to secretion of multiple cytokines and growth factors in breast cancer MDA-MB-231 cells

Hernández-Bedolla¹,

Carretero‐Ortega²,

Valadez-Sánchez³

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Breast cancer metastasis to the bone, potentially facilitated by chemotactic and angiogenic cytokines, contributes to a dramatic osteolytic effect associated with this invasive behavior. Based on the intrinsic ability of calcium sensing receptor (CaSR) to control hormonal secretion and considering its expression in the breast, we hypothesized that CaSR plays a chemotactic and proangiogenic role in highly invasive MDA-MB-231 breast cancer cells by promoting secretion of multiple cytokines. In this study, we show that MDA-MB-231 cells stimulated with R-568 calcimimetic and extracellular calcium secreted multiple cytokines and growth factors that induced endothelial cell migration and in vitro angiogenesis. These effects were dependent on the activity of CaSR as demonstrated by the inhibitory effect of either anti-CaSR blocking monoclonal antibodies or calcilytic NPS-2143. Moreover, CaSR knockdown prevented the proangiogenic effect of CaSR agonists. Importantly, CaSR promoted secretion of pleiotropic molecules like GM-CSF, EGF, MDC/CCL22, FGF-4 and IGFBP2, all known to be chemotactic mediators with putative angiogenic factor properties. In contrast, constitutive secretion of IL-6 and β-NGF was attenuated by CaSR. In the case of normal mammary cells, secretion of IL-6 was stimulated by CaSR, whereas a constitutive secretion of RANTES, Angiogenin and Oncostatin M was attenuated by this receptor. Taken together, our results indicate that an altered secretion of chemotactic and proangiogenic cytokines in breast cancer cells is modulated by CaSR, which can be considered a potential target in the therapy of metastatic breast cancer.

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“…This factor is an autocrine and/or paracrine growth factor required for multiple cellular events during embryogenesis [6]. It was previously found that FGF4 increases proliferation of neural progenitors [7] or bone marrow mesenchymal stem cells (BMMSCs) [8] and sustains the survival of trophoblast stem cells [9].…”

Section: Introductionmentioning

confidence: 99%

Fibroblast Growth Factor-4 Enhances Proliferation of Mouse Embryonic Stem Cells via Activation of c-Jun Signaling

et al. 2013

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Fibroblast growth factor-4 (FGF4) is expressed in embryonic stages and in adult tissues, where it plays critical roles in modulating multiple cellular functions. However, the exact roles of FGF4 on proliferation and differentiation of embryonic stem cells (ESCs) are not completely understood. Exogenous addition of FGF4 stimulated proliferation of mouse ESCs (mESCs), as proven by the increases in DNA synthesis and cell cycle regulatory protein induction. These increases were almost completely inhibited by pre-treating cells with anti-FGF4 antibody. FGF4 also activated c-Jun N-terminal kinase (JNK) and extracellular-signal regulated kinase (ERK) signaling, but not p38 kinase. Blockage of JNK signaling by SP600125 or by transfection with its specific siRNA significantly inhibited FGF4-stimulated cell proliferation through the suppression of c-Jun induction and activator protein-1 (AP-1) activity. However, ERK or p38 kinase inhibitor did not affect FGF4-stimulated proliferation in mESCs. FGF4 suppressed osteogenic differentiation of mESCs by inhibiting expression of transcription factors involved in bone formation. Further, exogenous FGF4 addition stimulated proliferation of human periodontal ligament stem cells (hPDLSCs) and bone marrow mesenchymal stem cells (BMMSCs) via activation of ERK signaling. FGF4 also augmented mineralization of hPDLSCs, but not of BMMSCs. Collectively, it is suggested that FGF4 triggers proliferation of stem cells by activating MAPK-mediated signaling, while it affects differently osteogenic differentiation according to the origins of stem cells.

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Pleiotropic function of FGF‐4: Its role in development and stem cells

Cited by 47 publications

References 132 publications

The changes of stemness biomarkers expression in human adipose‐derived stem cells during long‐term manipulation

The changes of stemness biomarkers expression in human adipose‐derived stem cells during long‐term manipulation

Chemotactic and proangiogenic role of calcium sensing receptor is linked to secretion of multiple cytokines and growth factors in breast cancer MDA-MB-231 cells

Fibroblast Growth Factor-4 Enhances Proliferation of Mouse Embryonic Stem Cells via Activation of c-Jun Signaling

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