Prosaposin: a new player in cell death prevention of U937 monocytic cells

Misasi, Roberta; Garofalo, Tina; Marzio, Luisa Di; Mattei, Vincenzo; Gizzi, Chiara; Hiraiwa, Masao; Pavan, Antonio; Cifone, Maria Grazia; Sorice, Maurizio

doi:10.1016/j.yexcr.2004.04.011

Cited by 28 publications

(25 citation statements)

References 47 publications

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“…Mutations in saposin C have been linked to lysosomal storage diseases such as Gaucher's disease (Horowitz and Zimran, 1994). Additionally, prosaposin and saposin C can act as neurotrophic factors in culture, bind to a putative G 0 -coupled cell surface receptor, and may be involved in the prevention of cell death Hiraiwa et al, 1997;Campana et al, 2000;Misasi et al, 2004). The region responsible for this "neuritogenic" effect is a 22 amino acid region within saposin C .…”

Section: Discussionmentioning

confidence: 99%

Progressive Deafness and Altered Cochlear Innervation in Knock-Out Mice Lacking Prosaposin

Akil¹,

Chang²,

Hiel³

et al. 2006

J. Neurosci.

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Section: Discussionmentioning

confidence: 99%

Progressive Deafness and Altered Cochlear Innervation in Knock-Out Mice Lacking Prosaposin

Akil¹,

Chang²,

Hiel³

et al. 2006

J. Neurosci.

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“…Next, purified liver-derived CD11b ϩ cells were thoroughly analyzed in terms of gene expression of aaM markers (43). RT-QPCR analysis revealed higher expression levels of genes associated with protection against oxidative burst (Sepp (44)), tissue repair and wound healing (F13a1, (45)), prevention of apoptosis (Psap, (46)) and down-regulation of inflammation (Mrc1, (47) in GPI-based treated/infected mice as compared with mock-treated/infected mice (Fig. 6c).…”

Section: Gpi-based Treatment Modulates the Macrophage Activation Statmentioning

confidence: 99%

A Glycosylphosphatidylinositol-Based Treatment Alleviates Trypanosomiasis-Associated Immunopathology

Stijlemans

Baral

Guilliams

et al. 2007

The Journal of Immunology

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The GPI-anchored trypanosome variant surface glycoprotein (VSG) triggers macrophages to produce TNF, involved in trypanosomiasis-associated inflammation and the clinical manifestation of sleeping sickness. Aiming at inhibiting immunopathology during experimental Trypanosoma brucei infections, a VSG-derived GPI-based treatment approach was developed. To achieve this, mice were exposed to the GPI before an infectious trypanosome challenge. This GPI-based strategy resulted in a significant prolonged survival and a substantial protection against infection-associated weight loss, liver damage, acidosis, and anemia; the latter was shown to be Ab-independent and correlated with reduced macrophage-mediated RBC clearance. In addition, GPI-based treatment resulted in reduced circulating serum levels of the inflammatory cytokines TNF and IL-6, abrogation of infection-induced LPS hypersensitivity, and an increase in circulating IL-10. At the level of trypanosomiasis-associated macrophage activation, the GPI-based treatment resulted in an impaired secretion of TNF by VSG and LPS pulsed macrophages, a reduced expression of the inflammatory cytokine genes TNF, IL-6, and IL-12, and an increased expression of the anti-inflammatory cytokine gene IL-10. In addition, this change in cytokine pattern upon GPI-based treatment was associated with the expression of alternatively activated macrophage markers. Finally, the GPI-based treatment also reduced the infection-associated pathology in Trypanosoma congolense and Trypanosoma evansi model systems as well as in tsetse fly challenge experiments, indicating potential field applicability for this intervention strategy.

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“…(18,20) Recent investigations show that PSAP could prevent cell death or apoptosis and promote cell survival. (21,22) Koochekpour et al (23) focus on the function of PSAP in prostate cancer and find PSAP is overexpressed in prostate cancer, and also upregulates androgen receptor (AR) and prostate specific antigen (PSA) expression and activity in prostate cancer cells.(24) Serum secreted PSAP levels significantly decrease in primary prostate cancer, but increase in metastatic prostate cancer. So it might be possible to take secreted PSAP in patients' serum as a bio-marker to differentiate primary and advanced prostate cancer.…”

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confidence: 99%

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confidence: 99%

Prosaposin, a regulator of estrogen receptor alpha, promotes breast cancer growth

Sun

et al. 2012

Cancer Science

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Prosaposin, a secreted protein, is a well-known pleiotropic growth factor. Although a previous report has indicated that prosaposin is overexpressed in breast cancer cell lines, the role of prosaposin in the development of breast cancer remains to be identified. Here, we first revealed that prosaposin upregulated estrogen receptor alpha expression, nuclear translocation and transcriptional activity by western blot, immunofluorescence assay and dual luciferase reporter gene assay, respectively. Furthermore, we demonstrated prosaposin upregulated estrogen receptor alpha expression through MAPK-signaling pathway using MAPK inhibitor. Proliferation assay and tumor xenograft experiments in nude mice (n = 6 per group) further confirmed prosaposin could promote breast cancer growth significantly in vitro and in vivo. These findings suggested that prosaposin might enhance estrogen receptor alpha-mediated signaling axis and play a role in breast cancer development and progression. (Cancer Sci 2012; 103: 1820-1825 B reast cancer is the most common malignancy and the main cause of death from cancers in women.(1) The carcinogenesis of breast cancer is frequently hormone-dependent. The female sex-steroid hormone estrogen 17b-estradiol (E2) plays a prominent role in mediating the maturation, proliferation, differentiation, and influences the growth and development of breast cancer.(2) Numerous studies have indicated that E2 can induce and promote breast cancer and this process is mediated primarily by estrogen receptor alpha (ERa). (3)(4)(5) Estrogen receptor (ER) is a member of the steroid/nuclear receptor family of transcription regulators, while ERa is the predominant receptor isoform expressed in breast cancer. Approximately 70% of breast cancer patients score positive for ERa at diagnosis.(6-9) Estrogen receptor alpha promotes cell growth, metastasis and also mediates resistance to apoptosis or immunosurveillance in breast cancer. (10)(11)(12) Prosaposin (PSAP) exists as a secretory protein (70 kDa) as well as a lysosomal protein (65 kDa). The molecular weight difference depends on the post-translational glycosylation. (13) Lysosomal PSAP is the precursor of four sphingolipid activator proteins (saposin A-D) and is involved in hydrolysis of sphingolipids within lysosome.(14) Secretory PSAP is a well-known pleiotropic growth factor found in secretory body fluid, such as seminal plasma, bile, cerebrospinal fluid, human milk, (15,16) as well as neuronal surface membrane.(17) The distribution of PSAP suggests it may have some specific extracellular functions. PSAP-deficiency in human and mice is lethal. (18,19) Prosaposin knock-out mice also present with a series of developmental abnormalities in the nervous system and male reproductive organs. (18,20) Recent investigations show that PSAP could prevent cell death or apoptosis and promote cell survival. (21,22) Koochekpour et al. (23) focus on the function of PSAP in prostate cancer and find PSAP is overexpressed in prostate cancer, and also upregulates androgen receptor (...

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Prosaposin: a new player in cell death prevention of U937 monocytic cells

Cited by 28 publications

References 47 publications

Progressive Deafness and Altered Cochlear Innervation in Knock-Out Mice Lacking Prosaposin

Progressive Deafness and Altered Cochlear Innervation in Knock-Out Mice Lacking Prosaposin

A Glycosylphosphatidylinositol-Based Treatment Alleviates Trypanosomiasis-Associated Immunopathology

Prosaposin, a regulator of estrogen receptor alpha, promotes breast cancer growth

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