Decreased Cyclic Inositol Phosphohydrolase Activity in Hamster Renal Tumors and Human Renal Cell Carcinomas

Sekar, Mahendran; Sambandam, Vijaya; Roy, Deodutta; Grizzle, William E.

doi:10.1006/bmme.1995.1064

Cited by 6 publications

(4 citation statements)

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“…This was in agreement with in-vitro studies that demonstrated high levels of lysophosphatidic acid, LPI, and their metabolites in tumor cells and transformed cells, as compared to their normal cell counterparts [7]. In some tumors, high extracellular levels of LPI and its metabolites have been observed due to decreased activity of the enzymes responsible for LPI catabolism [9, 10]. Indeed, signaling of lysophospholipid receptors is strongly reinforced in several tumors, as a consequence of receptor overexpression and/or increased availability of the relative ligands through their increased production or reduced degradation.…”

Section: Introductionsupporting

confidence: 87%

Peptide-guided targeting of GPR55 for anti-cancer therapy

et al. 2016

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Expression of the lysophosphatidylinositol receptor GPR55 correlates with invasive potential of metastatic cells and bone metastasis formation of different types of tumors. These findings suggest a role for GPR55 signaling in cancer progression, including in lymphoproliferative diseases. Here, we screened a M13-phage-displayed random library using the bait of HEK293 cells that heterologously expressed full-length HA-GPR55. We selected a set of phagotopes that carried 7-mer insert peptides flanked by a pair of cysteine residues, which resulted in cyclized peptides. Sequencing of selected phagotopes dictated the primary structure for the synthetic FITC-labeled peptide P1, which was analyzed for binding specificity to immunoprecipitated HA-GPR55, and to endogenously expressed GPR55, using cells interfered or not for GPR55, as well as for co-localization imaging with HA-GPR55 at the membrane level. The peptide P1 stimulated GPR55 endocytosis and inhibited GPR55-dependent proliferation of EHEB and DeFew cells, two human B-lymphoblastoid cell lines. Our data support the potential therapeutic application of peptide ligands of GPR55 for targeting and inhibiting growth of neoplastic cells, which overexpress GPR55 and are dependent on GPR55 signaling for their proliferation.

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Section: Introductionsupporting

confidence: 87%

Peptide-guided targeting of GPR55 for anti-cancer therapy

et al. 2016

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“…GPR55 is overexpressed in several tumour cells [23,60,61], with GPR55 expression shown to correlate with tumour aggressiveness [60] and GPR55 activation to promote cancer-cell proliferation both in cell culture and in xenografts in mice [62]. Therefore, we previously attempted to identify peptides that bind to human GPR55, for innovative targeting of GPR55 for potential therapeutic and/or diagnostic applications.…”

Section: Discussionmentioning

confidence: 99%

Peptide targeting of the lysolipid-sensing GPR55 for osteoclastogenesis tuning

Mosca¹,

Mangini²,

Barba³

et al. 2020

Preprint

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Background: The G-protein-coupled receptor GPR55 has been implicated in multiple biological activities, which has fuelled interest in its functional targeting. Its controversial pharmacology and the regulation often species dependent impacted the potential translation of preclinical data involving GPR55.Results: With the aim to identify novel GPR55 regulators, we have started investigating the lysophosphatidylinositol (LPI)-induced GPR55-mediated signal transduction. HeLa cells silenced for their endogenous receptor, by stable expression of a short-hairpin RNA specific for GPR55 5’-UTR, were the expression system for wild-type and mutated GPR55 that allowed the definition of the requirement of GPR55 Lys80 for LPI-induced MAPK activation and receptor internalisation. In RAW264.7 macrophages, GPR55 pathways were investigated by Gpr55 silencing using small-interfering RNAs, demonstrating that LPI increased intracellular Ca2+ levels and induced actin filopodium formation through GPR55 activation. Furthermore, LPI/GPR55 axis was shown to have an active role in the osteoclastogenesis of precursor RAW264.7 cells induced by the ‘receptor-activator of nuclear factor kappa-B ligand’ (RANKL). Indeed, this differentiation into mature osteoclasts was associated with 14-fold increase in Gpr55 mRNA levels. Moreover, GPR55 silencing or antagonism impaired the RANKL-induced transcription of the osteoclastogenesis markers: ‘nuclear factor of activated T-cells, cytoplasmic 1’, matrix metalloproteinase-9, cathepsin-K, tartrate-resistant acid phosphatase, and the calcitonin receptor, as evaluated by real-time PCR. Phage display was previously used to identify peptides that bind to GPR55. Here, the GPR55-specific peptide-P1 strongly inhibited osteoclast maturation of RAW264.7 macrophages.Conclusions: As bone-metastasis development can be blocked through inhibition of bone resorption, osteoclasts are strong targets for anti-metastatic treatments, and such GPR55-specific peptides might represent useful tools for novel therapeutic approaches.

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“…cIP/cIPH pathway has been implicated in regulating cell density [8]. Decreased cIPH activity has been reported in both renal [18] and hepatic tumors [21], which may account for the elevated level of cIP observed in the tumor [21]. Since cIP is a putative modulator of cell growth, the presence of the enzyme may indicate that regulation of cIP is important during this period of life.…”

Section: Discussionmentioning

confidence: 99%

“…The homogenate was spun at 10,000 g for 20 min, and clear supernatant used for cIPH activity. cIPH activity was performed with [ 3 H]cIP substrate as described earlier [17,18]. Ten microliters of cytosol or whole blood containing 150-1,000 Ìg protein was incubated with 10,000 dpm of cIP for 0, 30, 60 and 90 min at 37°C.…”

Section: Rabbit Ischemic Modelmentioning

confidence: 99%

Fetal and Placental Cyclic Inositol Phosphohydrolase in Normoxia and Hypoxia

Tan

Sekar²

1998

Neonatology

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Cyclic inositol phosphohydrolase (cIPH) converts cyclic inositol monophosphate (cIP), a putative modulator of cell growth, into inositol monophosphate. We hypothesized that hypoxic-ischemic injury alters cIPH activity in the placenta. On the 29th day of gestation pregnant rabbits were randomized to either 50 min of uterine ischemia (hypoxia) or no ischemia (controls). The activity of cIPH was measured by incubating with [³H]cIP and determining the release of [³H]inositol. Although no cIPH has been demonstrated in blood previously, cIPH activity was found in both fetal and maternal blood. cIPH activity was higher on the fetal side of the placenta than on the maternal side and was also higher in fetal blood compared to maternal blood. Hypoxia-ischemia failed to alter the cIPH activity in fetal blood and fetal and maternal placenta. Since cIPH activity is higher in the fetus and is retained even after major ischemia, modulation of cIP may be important in early development.

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Decreased Cyclic Inositol Phosphohydrolase Activity in Hamster Renal Tumors and Human Renal Cell Carcinomas

Cited by 6 publications

References 0 publications

Peptide-guided targeting of GPR55 for anti-cancer therapy

Peptide-guided targeting of GPR55 for anti-cancer therapy

Peptide targeting of the lysolipid-sensing GPR55 for osteoclastogenesis tuning

Fetal and Placental Cyclic Inositol Phosphohydrolase in Normoxia and Hypoxia

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