Proline-Rich Hypothalamic Polypeptide Has Opposite Effects on the Proliferation of Human Normal Bone Marrow Stromal Cells and Human Giant-cell Tumour Stromal Cells

Chailakhyan, R. K.; Gerasimov, Yu. V.; Chailakhyan, M. R.; Galoyan, A. A.

doi:10.1007/s11064-009-0113-7

Cited by 8 publications

(11 citation statements)

References 16 publications

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“…The goal of this study was the attempt to understand the mechanism of mesenchymal chondrosarcoma cell growth inhibition by PRP-1, taking into consideration its diverse metabolic and antitumorigenic properties [1][2][3][4][5][6][7][8][9][10][11][12][13], Chondrosarcoma is the second most common primary malignancy of bone, one that is locally invasive and potentially metastatic. Currently there Fig.…”

Section: Discussionmentioning

confidence: 99%

“…A combination of these two techniques has been recommended for genotoxicity testing to understand the mechanisms underlying mutagenicity. It was demonstrated recently that PRP-1 stimulates normal human marrow stromal cells but has an inhibitory effect on human giant cell tumor stromal cells [11]. Addition of PRP into bone marrow culture medium (irrespective of PRP concentration) resulted in a mean 1.5-fold increase in proliferation stimulation by day 4, that increased to 2.5-fold when the cultivation period was prolonged to 8 days.…”

Section: Introductionmentioning

confidence: 95%

“…This cytokine is also a mediator of the hypothalamus-neurohypophysis-bone marrow axis and a powerful immunomodulator [1,2]. Strong antibacterial (in vivo) and antiviral (in vitro) properties of hypothalamic proline rich peptides [3], anti neurodegenerative effects [4] and immunotropic properties [5] provide evidence for the existence of brain protective mechanisms against infection, neurodegeneration, immunodefficiencies [6] and tumors [7,8,[11][12][13]. We demonstrated that PRP-1 induced decay of tumor cells L929 and decreased mitotic activity of transformed mouse fibroblast cells, dose response growth inhibition of Jurkat cells, and inhibition of lymphosarcoma in vivo [1,7,8].…”

Section: Introductionmentioning

confidence: 99%

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Cytostatic Effect of the Hypothalamic Cytokine PRP-1 is Mediated by mTOR and cMyc Inhibition in High Grade Chondrosarcoma

2011

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This study aimed to further elucidate the molecular mechanisms of antiproliferative action of proline rich polypeptide 1 (PRP-1) cytokine, produced by neurosecretory cells of the hypothalamus to be considered as alternative adjuvant therapy for metastatic chondrosarcoma, which does not respond to chemotherapy or radiation and currently without any effective treatment. Rapid cell proliferation assay of human primary cultures from high grade chondrosarcoma patients biopsies and human chondrosarcoma JJ012 cell line indicated 50 and 80% inhibition in PRP-1 treated samples correspondingly. Videomicroscopy detected that despite the treatment there are still dividing cells, meaning that cells are not in the state of dormancy, rather PRP-1 repressed the cell cycle progression, exhibited cytostatic effect. The mammalian target of rapamycin (mTOR) is an intracellular serine/threonine protein kinase that has a crucial role in a nutrient sensitive signaling pathway that regulates cell growth. Experiments with mTOR pathway after PRP-1 (10 μg/ml) treatment indicated statistically significant 30% inhibition of mTOR activity and its 56% inhibition in immunoprecipitates with PRP-1 concentrations effective for cell proliferation inhibition. Treatment with PRP- caused inhibition of mTOR and downstream target cMyc oncogenic transcription factor sufficient to trigger the cytostatic effect in high grade, but not in low grade chondrosarcomas. The fact that lower concentrations than 10 μg/ml peptide with cytostatic effect did not inhibit mTOR, but inhibited cMyc prompted us to assume that PRP-1 binds to two different receptors facilitating the antiproliferative effect.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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Cytostatic Effect of the Hypothalamic Cytokine PRP-1 is Mediated by mTOR and cMyc Inhibition in High Grade Chondrosarcoma

2011

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“…Interestingly, PRP-1 demonstrated the inhibition of giant cell tumors of the bone and, conversely, supported the growth of human normal bone marrow stromal cells (31). Epigenetic regulation of miR302C expression (32) is defined by positive regulatory activity of JMJD2, H3K9me2 demethylase and NANOG in the promoter regions (28).…”

Section: Neuropeptides Involved In Epigenetic Control Of Cancermentioning

confidence: 99%

Epigenetic control of cancer by neuropeptides

Galoian

Patel

2016

Biomedical Reports

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Abstract. Neuropeptides act as neurohormones, neurotransmitters and/or neuromodulators. Neuropeptides maintain physiological homeostasis and are paramount in molecular mechanisms of disease progression and regulation, including in cancer. Neuropeptides, by their definition, originate and are secreted from the neuronal cells, they are able to signal to neighboring cells or are released into the blood flow, if they act as neurohormones. The majority of neuropeptides exert their functions through G protein-coupled receptors, with certain exceptions. Although previous studies indicate that neuropeptides function in supporting proliferation of malignant cells in many types of solid tumor, the antitumorigenic action of the neuropeptides and their receptors, for example, in gastric cancers and chondrosarcoma, were also reported. It is known that epigenetically modified chromatin regulates molecular mechanisms involved in gene expression and malignant progression. The epigenetic modifications are genetically heritable, although they do not cause changes in DNA sequence. DNA methylation, histone modifications and miRNA expression are subject to those modifications. While there is substantial data on epigenetic regulation of neuropeptides, the epigenetic control of cancer by neuropeptides is considered to be uncharted territory. The aim of the current review is to describe the involvement of neuropeptides in the epigenetic machinery of cancer based on data obtained from our laboratory and from other authors.

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“…E®ective methods were worked out to isolate these cells from the marrow and cultivate them in vitro, which provided for the increase in their numbers by more than 10 5 times. 16,17 Stromal progenitor cells, as well as their descendants have an enormous proliferation potential. 18 By the 10th passage the numbers of¯bro-blasts in some strains increase up to (1.2-7.2)Â10 9 cells.…”

Section: Introductionmentioning

confidence: 99%

Effect of acoustic pulses and EHF radiation on multipotent marrow stromal cells in tissue engineering constructs

Chailakhyan

Yusupov

Gorskaya

et al. 2017

J. Innov. Opt. Health Sci.

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In this paper, we studied the e®ects of physical factors, such as, acoustic pulses of laser-induced hydrodynamics (ALIH) and extremely-high frequencies (EHF) radiation, on the formation of heterotopic bone marrow organs. A suspension of precipitated bone marrow cells from CBA mice were exposed to ALIH pulses and EHF radiation separately and in their combination tissue engineering constructs, presenting gelatin sponges 2 by 2 by 2 mm in size containing 10 7 nucleated bone marrow cells, were exposed to physical factors and were implanted under the renal capsules of syngeneic mice. The newly formed hematopoietic organs were examined in three and¯ve months later after treatment. The¯ve months old transplants were bigger in size than the three months old transplants. The number of hematopoietic cells in the rest of the groups increased during this period by a factor from 3 to 10, the increase being as high as 20-fold in the ALIHþEHF group. Maximal concentration of multipotent stromal cells (MSCs) was in the ¶ Corresponding author. EHFþALIH, and minimal concentration was in the ALIHþEHF. The accumulation rate of bone capsule weight was highest for the transplants of EHFþALIH and ALIH-sponge groups during the¯rst three months. These data showed that the combined impact of the EHFþALIH on MSCs is the most e®ective for the formation of bone marrow transplantation.

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Proline-Rich Hypothalamic Polypeptide Has Opposite Effects on the Proliferation of Human Normal Bone Marrow Stromal Cells and Human Giant-cell Tumour Stromal Cells

Cited by 8 publications

References 16 publications

Cytostatic Effect of the Hypothalamic Cytokine PRP-1 is Mediated by mTOR and cMyc Inhibition in High Grade Chondrosarcoma

Cytostatic Effect of the Hypothalamic Cytokine PRP-1 is Mediated by mTOR and cMyc Inhibition in High Grade Chondrosarcoma

Epigenetic control of cancer by neuropeptides

Effect of acoustic pulses and EHF radiation on multipotent marrow stromal cells in tissue engineering constructs

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