2009
Vanhara, Petr; Lincová, Eva; Kozubík, Alois; Jurdic, Pierre; Soucek, Karel; Smarda, Jan
Growth/differentiation factor-15 inhibits differentiation into osteoclasts–a novel factor involved in control of osteoclast differentiation. Journal Article
In: Differentiation; research in biological diversity, vol. 78, no. 4, pp. 213–222, 2009, ISSN: 1432-0436 0301-4681, (Place: England).
Abstract | Links | BibTeX | Tags: Acid Phosphatase/metabolism, Animals, Calcitriol/pharmacology, Carbonic Anhydrase II/antagonists & inhibitors, Cathepsin K/antagonists & inhibitors/genetics, Cell Differentiation/*drug effects, Cell Line, Conditioned/pharmacology, Culture Media, Dose-Response Relationship, Drug, Femur/cytology, Growth Differentiation Factor 15/*pharmacology, Humans, Inbred Strains, Isoenzymes/metabolism, Macrophage Colony-Stimulating Factor/pharmacology, Macrophages/cytology, Male, Mice, NF-kappa B/antagonists & inhibitors, Osteoclasts/*drug effects/metabolism, Prostatic Neoplasms/metabolism, Proto-Oncogene Proteins c-fos/antagonists & inhibitors, RANK Ligand/pharmacology, Tartrate-Resistant Acid Phosphatase, Time Factors, Tumor
@article{vanhara_growthdifferentiation_2009,
title = {Growth/differentiation factor-15 inhibits differentiation into osteoclasts–a novel factor involved in control of osteoclast differentiation.},
author = {Petr Vanhara and Eva Lincová and Alois Kozubík and Pierre Jurdic and Karel Soucek and Jan Smarda},
doi = {10.1016/j.diff.2009.07.008},
issn = {1432-0436 0301-4681},
year = {2009},
date = {2009-11-01},
journal = {Differentiation; research in biological diversity},
volume = {78},
number = {4},
pages = {213–222},
abstract = {Survival and capability of cancer cells to form metastases fundamentally depend on interactions with their microenvironment. Secondary tumors originating from prostate carcinomas affect remodeling of bone tissue and can induce both osteolytic and osteocondensing lesions. However, particular molecular mechanisms responsible for selective homing and activity of cancer cells in bone microenvironment have not been clarified yet. Growth/differentiation factor-15 (GDF-15), a distant member of the TGF-beta protein family, has recently been associated with many human cancers, including prostate. We show that both pure GDF-15 and the GDF-15-containing growth medium of 1,25(OH)(2)-vitamin D(3)-treated prostate adenocarcinoma LNCaP cells suppress formation of mature osteoclasts differentiated from RAW264.7 macrophages and bone-marrow precursors by M-CSF/RANKL in a dose-dependent manner. GDF-15 inhibits expression of c-Fos and activity of NFkappaB by delayed degradation of IkappaB. Moreover, GDF-15 inhibits expression of carbonic anhydrase II and cathepsin K, key osteoclast enzymes, and induces changes in SMAD and p38 signaling. The lack of functional osteoclasts can contribute to accumulation of bone matrix by reduction of bone resorption. These results unveil new role of GDF-15 in modulation of osteoclast differentiation and possibly in therapy of bone metastases.},
note = {Place: England},
keywords = {Acid Phosphatase/metabolism, Animals, Calcitriol/pharmacology, Carbonic Anhydrase II/antagonists & inhibitors, Cathepsin K/antagonists & inhibitors/genetics, Cell Differentiation/*drug effects, Cell Line, Conditioned/pharmacology, Culture Media, Dose-Response Relationship, Drug, Femur/cytology, Growth Differentiation Factor 15/*pharmacology, Humans, Inbred Strains, Isoenzymes/metabolism, Macrophage Colony-Stimulating Factor/pharmacology, Macrophages/cytology, Male, Mice, NF-kappa B/antagonists & inhibitors, Osteoclasts/*drug effects/metabolism, Prostatic Neoplasms/metabolism, Proto-Oncogene Proteins c-fos/antagonists & inhibitors, RANK Ligand/pharmacology, Tartrate-Resistant Acid Phosphatase, Time Factors, Tumor},
pubstate = {published},
tppubtype = {article}
}
Survival and capability of cancer cells to form metastases fundamentally depend on interactions with their microenvironment. Secondary tumors originating from prostate carcinomas affect remodeling of bone tissue and can induce both osteolytic and osteocondensing lesions. However, particular molecular mechanisms responsible for selective homing and activity of cancer cells in bone microenvironment have not been clarified yet. Growth/differentiation factor-15 (GDF-15), a distant member of the TGF-beta protein family, has recently been associated with many human cancers, including prostate. We show that both pure GDF-15 and the GDF-15-containing growth medium of 1,25(OH)(2)-vitamin D(3)-treated prostate adenocarcinoma LNCaP cells suppress formation of mature osteoclasts differentiated from RAW264.7 macrophages and bone-marrow precursors by M-CSF/RANKL in a dose-dependent manner. GDF-15 inhibits expression of c-Fos and activity of NFkappaB by delayed degradation of IkappaB. Moreover, GDF-15 inhibits expression of carbonic anhydrase II and cathepsin K, key osteoclast enzymes, and induces changes in SMAD and p38 signaling. The lack of functional osteoclasts can contribute to accumulation of bone matrix by reduction of bone resorption. These results unveil new role of GDF-15 in modulation of osteoclast differentiation and possibly in therapy of bone metastases.
Procházková, Jirina; Stixová, Lenka; Soucek, Karel; Hofmanová, Jirina; Kozubík, Alois
In: European journal of haematology, vol. 83, no. 1, pp. 35–47, 2009, ISSN: 1600-0609 0902-4441, (Place: England).
Abstract | Links | BibTeX | Tags: Acute/*drug therapy/metabolism/*pathology, Amino Acid Chloromethyl Ketones/pharmacology, Apoptosis/*drug effects/physiology, Caspase Inhibitors, Caspases/metabolism, Cell Differentiation/drug effects, Cysteine Proteinase Inhibitors/pharmacology, Enzyme Activation/drug effects, HL-60 Cells, Humans, Indoles/*pharmacology, Leukemia, Lipoxygenase Inhibitors/pharmacology, MAP Kinase Signaling System/drug effects, Monocytes/*drug effects/pathology, NF-kappa B/antagonists & inhibitors, Promyelocytic, Tumor Necrosis Factor-alpha/*pharmacology
@article{prochazkova_monocytic_2009,
title = {Monocytic differentiation of leukemic HL-60 cells induced by co-treatment with TNF-alpha and MK886 requires activation of pro-apoptotic machinery.},
author = {Jirina Procházková and Lenka Stixová and Karel Soucek and Jirina Hofmanová and Alois Kozubík},
doi = {10.1111/j.1600-0609.2009.01240.x},
issn = {1600-0609 0902-4441},
year = {2009},
date = {2009-07-01},
journal = {European journal of haematology},
volume = {83},
number = {1},
pages = {35–47},
abstract = {The block of hematopoietic differentiation program in acute myeloid leukemia cells can be overcome by differentiating agent like retinoic acid, but it has several side effects. A study of other differentiation signaling pathways is therefore useful to predict potential targets of anti-leukemic therapy. We demonstrated previously that the co-treatment of HL-60 cells with Tumor necrosis factor-alpha (TNF-alpha) (1 ng/mL) and inhibitor of 5-lipoxygenase MK886 (5 microm) potentiated both monocytic differentiation and apoptosis. In this study, we detected enhanced activation of three main types of mitogen-activated protein kinases (MAPKs) (p38, c-Jun amino-terminal kinase [JNK], extracellular signal-regulated kinase [ERK]), so we assessed their role in differentiation using appropriate pharmacologic inhibitors. The inhibition of pro-apoptotic MAPKs (p38 and JNK) suppressed the effect of MK886 + TNF-alpha co-treatment. On the other hand, down-regulation of pro-survival ERK pathway led to increased differentiation. Those effects were accompanied by increased activation of caspases in cells treated by MK886 + TNF-alpha. Pan-caspase inhibitor ZVAD-fmk significantly decreased both number of apoptotic and differentiated cells. The same effect was observed after inhibition of caspase 9, but not caspase 3 and 8. To conclude, we evidenced that the activation of apoptotic processes and pathways supporting apoptosis (p38 and JNK MAPKs) is required for the monocytic differentiation of HL-60 cells.},
note = {Place: England},
keywords = {Acute/*drug therapy/metabolism/*pathology, Amino Acid Chloromethyl Ketones/pharmacology, Apoptosis/*drug effects/physiology, Caspase Inhibitors, Caspases/metabolism, Cell Differentiation/drug effects, Cysteine Proteinase Inhibitors/pharmacology, Enzyme Activation/drug effects, HL-60 Cells, Humans, Indoles/*pharmacology, Leukemia, Lipoxygenase Inhibitors/pharmacology, MAP Kinase Signaling System/drug effects, Monocytes/*drug effects/pathology, NF-kappa B/antagonists & inhibitors, Promyelocytic, Tumor Necrosis Factor-alpha/*pharmacology},
pubstate = {published},
tppubtype = {article}
}
The block of hematopoietic differentiation program in acute myeloid leukemia cells can be overcome by differentiating agent like retinoic acid, but it has several side effects. A study of other differentiation signaling pathways is therefore useful to predict potential targets of anti-leukemic therapy. We demonstrated previously that the co-treatment of HL-60 cells with Tumor necrosis factor-alpha (TNF-alpha) (1 ng/mL) and inhibitor of 5-lipoxygenase MK886 (5 microm) potentiated both monocytic differentiation and apoptosis. In this study, we detected enhanced activation of three main types of mitogen-activated protein kinases (MAPKs) (p38, c-Jun amino-terminal kinase [JNK], extracellular signal-regulated kinase [ERK]), so we assessed their role in differentiation using appropriate pharmacologic inhibitors. The inhibition of pro-apoptotic MAPKs (p38 and JNK) suppressed the effect of MK886 + TNF-alpha co-treatment. On the other hand, down-regulation of pro-survival ERK pathway led to increased differentiation. Those effects were accompanied by increased activation of caspases in cells treated by MK886 + TNF-alpha. Pan-caspase inhibitor ZVAD-fmk significantly decreased both number of apoptotic and differentiated cells. The same effect was observed after inhibition of caspase 9, but not caspase 3 and 8. To conclude, we evidenced that the activation of apoptotic processes and pathways supporting apoptosis (p38 and JNK MAPKs) is required for the monocytic differentiation of HL-60 cells.