FGF-3 and FGF-4 elicit distinct oncogenic properties in mouse mammary myoepithelial cells

Hajitou, Amin; Baramova, Eugenia N.; Bajou, Khalid; Noë, Veerle; Bruyneel, Erik; Mareel, Marc; Collette, Julien; Foidart, Jean‐Michel; Calberg-Bacq, Claire-Michelle

doi:10.1038/sj.onc.1202126

Cited by 28 publications

(17 citation statements)

References 38 publications

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“…[37][38][39] Furthermore, some genes such as FGF-3 and rsc (rabbit squamous cell carcinoma) have potent oncogenic activities in nude mice, but do not induce anchorage-independent growth in the semi-solid media. 36,40,41) HDGF seems to belong to this group. Although NIH3T3-HDGF stable transfectants could not form large colonies in semi-solid media, but they did form more small colonies than the mock or parent cells in the soft agar assay.…”

Section: Discussionmentioning

confidence: 99%

Hepatoma‐derived growth factor induces tumorigenesis in vivo through both direct angiogenic activity and induction of vascular endothelial growth factor

et al. 2003

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Hepatoma-derived growth factor (HDGF) is highly expressed in tumor cells, and stimulates their proliferation. In the present study, we investigated the role of HDGF in tumorigenesis and elucidated the mechanism of action. Stable transfectants of NIH3T3 cells overexpressing HDGF did not show significant anchorage-independent growth in soft agar assay. However, these stable transfectants overexpressing HDGF generated sarcomatous tumors in nude mice. These tumors were red-colored macroscopically, and histologically showed a rich vascularity. Immunohistochemical analysis using CD31 antibody showed new vessel formation. Recombinant HDGF stimulated proliferation of human umbilical vein endothelial cells in a dose-dependent manner, and stimulated tubule formation. ncogenesis is induced by genetic alterations of various proteins involved in the cell cycle and cellular proliferation, especially by up-regulation of oncogenic genes and/or down-regulation of tumor suppressor genes. Overexpression of growth factors, receptors for growth factors, proteins related to signal transduction from the respective receptors and positive transcriptional regulatory factors, and suppressed expression of growth-inhibitory genes, including negative signal transducers and transcriptional regulatory factors, have all been associated with tumor formation in nude mice. [1][2][3][4][5][6][7][8][9] Hepatoma-derived growth factor (HDGF) is a heparin-binding protein purified from the conditioned media of Huh-7 hepatoma cells, which proliferate autonomously in a serum-free chemically defined medium.10, 11) HDGF contains a well-conserved N-terminal amino acid sequence, which is called the hath (homologous to amino terminus of HDGF) region. 11,12) HDGF is translocated to the nucleus via nuclear localization signals and its nuclear translocation is essential for induction of cell growth activity. 13,14) It is highly expressed in fetal tissues and may be involved in development of organs, including the cardiovascular system, kidney and liver. [15][16][17][18] HDGF has mitogenic activity for some hepatocellular carcinoma (HCC) cells, in addition to fibroblasts, endothelial cells, vascular smooth muscle cells and fetal hepatocytes. 10,11,13,15,16,18,19) It is abundantly expressed in tumor cell lines, and HDGF antisense oligonucleotides suppress the proliferation of hepatoma cells expressing HDGF endogenously. 19) In human and murine models of HCC, HDGF expression increases at an early stage, even before tumor formation. Furthermore, HDGF is more abundantly expressed in HCC than in adjacent non-tumor liver tissues.20) HDGF is a unique nuclear/growth factor, possibly playing an important role in the development and progression of cancer cells.Increasing evidence suggests that HDGF might be implicated in tumorigenesis. However, whether HDGF really induces transformation of cells and tumor formation in vivo is not known. Therefore, we established stable cell lines overexpressing HDGF from NIH3T3 fibroblasts by transfection, and investigated their oncogenic p...

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Section: Discussionmentioning

confidence: 99%

Hepatoma‐derived growth factor induces tumorigenesis in vivo through both direct angiogenic activity and induction of vascular endothelial growth factor

et al. 2003

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“…We found that FGF-3 exerts a specific effect, which differs from the mode of action of FGF-4, a known oncogenic product [22]. The present work was thus undertaken to investigate what was the effect of an fgf-3 expression in human mammary cells.…”

Section: Introductionmentioning

confidence: 98%

Progression in MCF-7 breast cancer cell tumorigenicity: compared effect of FGF-3 and FGF-4

Hajitou

Deroanne

Noël

et al. 2000

Breast Cancer Res Treat

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SummaryThe transforming properties of fibroblast growth factor 3 (FGF-3) were investigated in MCF7 breast cancer cells and compared to those of FGF-4, a known oncogenic product. The short form of fgf-3 and the fgf-4 sequences were each introduced with retroviral vectors and the proteins were only detected in the cytoplasm of the infected cells, as expected. In vitro, cells producing FGF-3 (MCF7.fgf-3) and FGF-4 (MCF7.fgf-4) displayed an amount of estrogen receptors decreased to around 45% of the control value. However, MCF7.fgf-3 cell proliferation remained responsive to estradiol supply. The sensitivity of the MCF7.fgf-4 cells, if existant, was masked by the important mitogenic action exerted by FGF-4. In vivo, the MCF7.fgf-3 and MCF7.fgf-4 cells gave rise to tumors under conditions in which the control cells were not tumorigenic. Supplementing the mice with estrogen had the paradoxical effect of totally suppressing the start of the FGF-3 as well as the FGF-4 tumors. Tumorigenicity in the presence of matrigel was similar for MCF7.fgf-3 and control cells and was increased by estrogen supplementation. Once started, the MCF7.fgf-4 tumors grew with a characteristic high rate. Remarkably, FGF-4 but not FGF-3, stimulated the secretion of vascular endothelial growth factor (VEGF 165 ) without altering the steady-state level of its mRNA, suggesting a possible regulation of VEGF synthesis at the translational level in MCF7 cells. The increased VEGF secretion is probably involved in the more aggressive phenotype of the MCF7.fgf-4 cells while a decreased dependence upon micro-environmental factors might be part of the increased tumorigenic potential of the MCF7.fgf-3 cells.

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“…AAVP-transduced HSVtk also may act as a cell suicide-inducing gene in the presence of ganciclovir (GCV), which is converted by the thymidine kinase enzyme to a cytotoxic compound (36). To investigate the efficacy of the GRP78-targeting AAVP in breast cancer treatment, we used the syngeneic EF43.fgf4 mammary tumor model (25,37). Five days after tumor cell implantation, mice received an i.v.…”

Section: Grp78 Is Strongly Expressed In Human Ibcmentioning

confidence: 99%

Towards a transcriptome-based theranostic platform for unfavorable breast cancer phenotypes

Dobroff

D’Angelo

Eckhardt

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Inflammatory breast carcinoma (IBC) is one of the most lethal forms of human breast cancer, and effective treatment for IBC is an unmet clinical need in contemporary oncology. Tumor-targeted theranostic approaches are emerging in precision medicine, but only a few specific biomarkers are available. Here we report up-regulation of the 78-kDa glucose-regulated protein (GRP78) in two independent discovery and validation sets of specimens derived from IBC patients, suggesting translational promise for clinical applications. We show that a GRP78-binding motif displayed on either bacteriophage or adeno-associated virus/phage (AAVP) particles or loop-grafted onto a human antibody fragment specifically targets orthotopic IBC and other aggressive breast cancer models in vivo. To evaluate the theranostic value, we used GRP78-targeting AAVP particles to deliver the human Herpes simplex virus thymidine kinase type-1 (HSVtk) transgene, obtaining simultaneous in vivo diagnosis through PET imaging and tumor treatment by selective activation of the prodrug ganciclovir at tumor sites. Translation of this AAVP system is expected simultaneously to image, monitor, and treat the IBC phenotype and possibly other aggressive (e.g., invasive and/or metastatic) subtypes of breast cancer, based on the inducible cell-surface expression of the stress-response chaperone GRP78, and possibily other cell-surface receptors in human tumors.inflammatory breast cancer | ligand-directed theranostics | molecular imaging | gene therapy | AAVP B reast cancer remains a major cause of cancer death in women (1), and one of its most lethal presentations is inflammatory breast carcinoma (IBC), a clinicopathological diagnosis characterized by diffuse erythema/edema involving the skin of the breast (a sign classically known as "peau d'orange") caused by tumor emboli within the dermal lymphatics. Although IBC comprises <5% of breast cancer cases, the tumor accounts for more than 10% of breast cancer mortality in the United States (2, 3). IBC is considered aggressive because it evolves rapidly-over days to weeks rather than months-with most patients presenting with lymph node involvement and more than 30% of patients having distant metastases at diagnosis (4, 5). Although IBC, like non-IBC breast cancers, is a heterogeneous disease and can occur as any of the five molecular subtypes, the IBC is most commonly ErbB2 overexpressing or triple negative (6), thus rendering a large armamentarium of targeted drugs ineffective. Finally, IBC generally presents with high-grade histology, elevated cell proliferation rate, and angiolymphatic invasion (5, 7). Indeed, the hallmark lymphatic invasion dictates the requirement for initial systemic treatment of IBC, because micrometastatic disease likely has occurred even in the Significance Inflammatory breast cancer (IBC) is defined clinically and pathologically. Dermal lymphatic invasion is typical but is neither necessary nor sufficient for diagnosis; sentinel lymph node biopsy is contraindicated, challenging multidisciplinar...

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FGF-3 and FGF-4 elicit distinct oncogenic properties in mouse mammary myoepithelial cells

Cited by 28 publications

References 38 publications

Hepatoma‐derived growth factor induces tumorigenesis in vivo through both direct angiogenic activity and induction of vascular endothelial growth factor

Hepatoma‐derived growth factor induces tumorigenesis in vivo through both direct angiogenic activity and induction of vascular endothelial growth factor

Progression in MCF-7 breast cancer cell tumorigenicity: compared effect of FGF-3 and FGF-4

Towards a transcriptome-based theranostic platform for unfavorable breast cancer phenotypes

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