PLAB, a novel placental bone morphogenetic protein

Hromas, Robert; Hufford, Matthew B.; Sutton, Joanne; Xu, Dawei; Li, Yunxing; Lü, Li

doi:10.1016/s0167-4781(97)00122-x

Cited by 201 publications

(151 citation statements)

References 16 publications

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“…It was first named macrophageinhibiting cytokine 1 (Bootcov et al 1997) or placental bone morphogenetic protein (Hromas et al 1997), and also later named prostate-derived factor (Paralkar et al 1998) or non-steroidal anti-inflammatory drug-activated gene (Baek et al 2001). GDF15 is abundantly expressed in placenta and mildly expressed in liver and prostate at baseline, but many tissues show the dramatic induction of expression following various stimuli such as cytokine, growth factor, or hypoxia (Bootcov et al 1997, Albertoni et al 2002, Nazarova et al 2004, Schlittenhardt et al 2004.…”

Section: Discussionmentioning

confidence: 99%

Vitamin K2 induces phosphorylation of protein kinase A and expression of novel target genes in osteoblastic cells

Ichikawa

Horie‐Inoue²,

Ikeda³

et al. 2007

Journal of Molecular Endocrinology

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Vitamin K is known as a critical nutrient required for bone homeostasis and blood coagulation, and it is clinically used as a therapeutic agent for osteoporosis in Japan. Besides its enzymatic action as a cofactor of vitamin K-dependent g-glutamyl carboxylase (GGCX), we have previously shown that vitamin K 2 is a transcriptional regulator of bone marker genes and extracellular matrix-related genes, by activating the steroid and xenobiotic receptor (SXR). To explore a novel action of vitamin K in osteoblastic cells, we identified genes up-regulated by a vitamin K 2 isoform menaquinone-4 (MK-4) using oligonucleotide microarray analysis. Among these up-regulated genes by MK-4, growth differentiation factor 15 (GDF15) and stanniocalcin 2 (STC2) were identified as novel MK-4 target genes independent of GGCX and SXR pathways in human and mouse osteoblastic cells. The induction of GDF15 and STC2 is likely specific to MK-4, as it was not exerted by another vitamin K 2 isoform MK-7, vitamin K 1 , or the MK-4 side chain structure geranylgeraniol. Investigation of the involved signaling pathways revealed that MK-4 enhanced the phosphorylation of protein kinase A (PKA), and the MK-4-dependent induction of both GDF15 and STC2 genes was reduced by the treatment with a PKA inhibitor H89 or siRNA against PKA. These results suggest that vitamin K 2 modulates its target gene expression in osteoblastic cells through the PKA-dependent mechanism, which may be distinct from the previously known vitamin K signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Vitamin K2 induces phosphorylation of protein kinase A and expression of novel target genes in osteoblastic cells

Ichikawa

Horie‐Inoue²,

Ikeda³

et al. 2007

Journal of Molecular Endocrinology

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“…DISCUSSION GDF15 is a divergent member of human TGF-β superfamily that displays similarity to both classical TGF-β isoforms and bone morphogenetic proteins (BMPs). 22 GDF15, also known as macrophage inhibitory cytokine 1 (MIC-1), nonsteroidal anti-inflammatory drug-activated gene (NAG-1), prostate-derived factor (PDF), placental bone morphogenetic protein (PLAB), and placental TGF-β (PTGF-β), [23][24][25][26] has GDF15 in the tumor microenvironment of ESCC N Urakawa et al Figure 2 Expression of GDF15 in PBMo-derived macrophages stimulated with TECM and ESCC cell lines. (a) mRNA expression of GDF15 in PBMo-derived macrophages stimulated with TECM and ESCC cell lines.…”

Section: Gdf15 Increased the Growth Of The Escc Cell Lines By Triggermentioning

confidence: 99%

GDF15 derived from both tumor-associated macrophages and esophageal squamous cell carcinomas contributes to tumor progression via Akt and Erk pathways

Urakawa

Utsunomiya

Nishio

et al. 2015

Laboratory Investigation

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Tumor-associated macrophages (TAMs) are known to be involved in the progression, angiogenesis, and motility of various cancers. We previously reported the association between an increased number of infiltrating TAMs with tumor progression and poor prognosis in esophageal squamous cell carcinomas (ESCCs). To study the roles of TAMs in ESCC, we first exposed peripheral blood monocyte (PBMo)-derived macrophages from healthy volunteers to conditioned media of TE series human ESCC cell line (TECM) and confirmed the induction of the expression of the M2 macrophage marker CD204 and the protumorigenic factors interleukin (IL)-10, VEGFA, and MMPs. Next, we compared gene expression profiles between PBModerived macrophages stimulated with or without TECM by cDNA microarray and focused on growth differentiation factor 15 (GDF15) among the highly expressed genes including IL-6, IL-8, and CXCL1. Our immunohistochemical study of 70 surgically resected ESCCs revealed that GDF15 was present not only in cancer cells but also in macrophages. The high expression of GDF15 in the ESCCs was significantly correlated with several more malignant phenotypes including vessel invasion, lymph node metastasis, and clinical stages. Patients with high GDF15 expression showed significantly poorer disease-free survival (P = 0.011) and overall survival (P = 0.041). We also found that recombinant human GDF15 promotes cell proliferation and the phosphorylation of both Akt and Erk1/2 in ESCC cell lines in vitro. These results indicate that GDF15 is secreted by both TAMs and cancer cells in the tumor microenvironment and is associated with aberrant growth and a poor prognosis in human ESCC.

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“…The protein encoded by NAG-1, which has been isolated by a variety of cloning strategies, is also known as macrophage inhibitory cytokine-1 (MIC-1) (Bootcov et al, 1997), placental transforming growth factor β (PTGFB) (Tan et al, 2000), prostate derived factor (PDF) (Paralkar et al, 1998), growth differentiation factor 15 (GDF15) (Hsiao et al, 2000) and placental bone morphogenetic protein (PLAB) (Hromas et al, 1997). The diversity of biological functions indicated by this nomenclature suggests that the biological role of the NAG-1 protein depends on cell context.…”

Section: Introductionmentioning

confidence: 99%

Molecular characterisation of canine nonsteroidal anti-inflammatory drug-activated gene (NAG-1)

Yamaguchi

Whitlock

Liggett

et al. 2008

The Veterinary Journal

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Nonsteroidal anti-inflammatory drug (NSAID)-activated gene (NAG-1), a divergent member of the transforming growth factor β superfamily, was previously identified as a gene induced by several anti-tumorigenic compounds, including NSAIDs and peroxisome proliferator-activated receptor γ (PPARγ) ligands in humans. In this study, canine NAG-1 was characterised from a canine genomic database. Gene induction by some NSAIDs and PPARγ ligands was demonstrated in canine osteosarcoma cell lines. Phylogenetic analysis indicates that canine NAG-1 is more homologous with the corresponding mouse and rat genes than with human NAG-1. Expression of canine NAG-1 was increased by treatment with piroxicam and SC-560 (NSAIDs) and the PPARγ ligand rosiglitazone. This study demonstrates that canine NAG-1 is up-regulated by some anti-tumorigenic compounds in osteosarcoma cell lines and may provide an important target of chemotherapy in canine cancer.

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PLAB, a novel placental bone morphogenetic protein

Cited by 201 publications

References 16 publications

Vitamin K2 induces phosphorylation of protein kinase A and expression of novel target genes in osteoblastic cells

Vitamin K2 induces phosphorylation of protein kinase A and expression of novel target genes in osteoblastic cells

GDF15 derived from both tumor-associated macrophages and esophageal squamous cell carcinomas contributes to tumor progression via Akt and Erk pathways

Molecular characterisation of canine nonsteroidal anti-inflammatory drug-activated gene (NAG-1)

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