Substance P receptor in U373 MG human astrocytoma cells activates mitogen-activated protein kinases ERK1/2 through Src

Yamaguchi, Kazuya; Kugimiya, Toyoki; Miyazaki, Tatsuya

doi:10.1007/s10014-005-0178-1

Cited by 23 publications

(18 citation statements)

References 31 publications

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“…TACR1 is a G protein-coupled receptor which is upregulated in the joint tissues of patients with painful OA [41]. SRC, a tyrosine kinase, plays a role in substance P signaling which has been implicated in many inflammatory diseases [42, 43]. These findings together indicate that PC is potentially an analgesic agent.…”

Section: Discussionmentioning

confidence: 99%

Phosphocitrate Is Potentially a Disease-Modifying Drug for Noncrystal-Associated Osteoarthritis

Sun

Mauerhan

Franklin

et al. 2013

BioMed Research International

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Phosphocitrate (PC), a calcification inhibitor, inhibits the development of crystal-associated osteoarthritis (OA) in Hartley guinea pigs. However, the molecular mechanisms underlying its disease-modifying effect remain elusive. This study sought to test the hypothesis that PC has calcium crystal-independent biological activities which are, at least in part, responsible for its disease-modifying activity. We found that PC inhibited the proliferation of OA fibroblast-like synoviocytes in the absence of calcium crystals. Consistent with its effect on cell proliferation, PC downregulated the expression of numerous genes classified in cell proliferation. PC also downregulated the expression of many genes classified in angiogenesis and inflammatory response including prostaglandin-endoperoxide synthase 2, interleukin-1 receptor, type I, and chemokine (C-C motif) ligand 2. In contrast, PC upregulated the expression of many genes classified in musculoskeletal tissue development, including aggrecan, type I collagen, and insulin-like growth factor binding protein 5. These findings suggest that PC is not only a promising disease-modifying drug for crystal-associated OA but also for noncrystal-associated OA.

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Section: Discussionmentioning

confidence: 99%

Phosphocitrate Is Potentially a Disease-Modifying Drug for Noncrystal-Associated Osteoarthritis

Sun

Mauerhan

Franklin

et al. 2013

BioMed Research International

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“…For example, recent data suggest that ERK1/2 in GBM cells is activated by substance P receptor (SPR) and several other mitogenic G protein-coupled receptors (GPCRs) including α(1B)-adrenergic, M(3)-muscarinic and H(1)-histaminergic in an Src-dependent manner. Furthermore, blockade of EGFR, which is transactivated by SPR, has a minimal effect on SPR-mediated ERK1/2 phosphorylation [21]. In addition, Gab1/Shp2 and Ras/ERK1-2 in concert become independent of PI3K upon strong EGFR stimulation and dependent on PI3K upon limited EGFR activation.…”

Section: Preclinical Data On Egfr Inhibition In Gliomasmentioning

confidence: 97%

Epidermal growth factor receptor and glioblastoma multiforme: molecular basis for a new approach

et al. 2008

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High-grade gliomas are the most common primary malignant brain tumours. Surgery, radiotherapy and chemotherapy are the cornerstone of actual treatment. In spite of large therapeutic efforts, overall survival is still poor. New molecular data allow a new molecular classification for high-grade gliomas and open a therapeutic window for targeted therapy. Molecular diagnostic tools may provide a basis for receptor-based therapies and enough information to personalise future treatments. In this regard, epidermal growth factor receptor (EGFR) is a target that will play a critical role in the management of glioma patients. This review summarises basic and preclinical data that support future use of therapies against EGFR.

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“…SRC is a key downstream intermediate of growth factor receptors frequently overexpressed in brain tumors, including EGFR and platelet-derived growth factor receptor (PDGFR), allowing, in association with FAK kinase, cytoskeletal-linked cell survival and migration (6). In preclinical models of glioblastoma, genetic and pharmacologic blockade of SRC resulted effective in inhibiting proliferation and invasion (7,8).…”

Section: Introductionmentioning

confidence: 99%

Suppression of SRC Signaling Is Effective in Reducing Synergy between Glioblastoma and Stromal Cells

Calgani

Vignaroli

Zamperini

et al. 2016

Molecular Cancer Therapeutics

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Glioblastoma cells efficiently interact with and infiltrate the surrounding normal tissue, rendering surgical resection and adjuvant chemo/radiotherapy ineffective. New therapeutic targets, able to interfere with glioblastoma's capacity to synergize with normal brain tissue, are currently under investigation. The compound Si306, a pyrazolo[3,4-d]pyrimidine derivative, selected for its favorable activity against SRC, was tested in vitro and in vivo on glioblastoma cell lines. In vivo, combination treatment with Si306 and radiotherapy was strongly active in reducing U-87 xenograft growth with respect to control and single treatments. The histology revealed a significant difference in the stromal compartment of tumoral tissue derived from control or radiotherapy-treated samples with respect to Si306-treated samples, showing in the latter a reduced presence of collagen and a-SMA-positive cells. This effect was paralleled in vitro by the capacity of Si306 to interfere with myofibroblastic differentiation of normal fibroblasts induced by U-87 cells. In the presence of Si306, TGF-b released by U-87 cells, mainly in hypoxia, was ineffective in upregulating a-SMA and b-PDGFR in fibroblasts. Si306 efficiently reached the brain and significantly prolonged the survival of mice orthotopically injected with U-87 cells. Drugs that target SRC could represent an effective therapeutic strategy in glioblastoma, able to block positive paracrine loop with stromal cells based on the b-PDGFR axis and the formation of a tumor-promoting microenvironment. This approach could be important in combination with conventional treatments in the effort to reduce tumor resistance to therapy. Mol Cancer Ther; 15(7); 1535-44. Ó2016 AACR.

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Substance P receptor in U373 MG human astrocytoma cells activates mitogen-activated protein kinases ERK1/2 through Src

Cited by 23 publications

References 31 publications

Phosphocitrate Is Potentially a Disease-Modifying Drug for Noncrystal-Associated Osteoarthritis

Phosphocitrate Is Potentially a Disease-Modifying Drug for Noncrystal-Associated Osteoarthritis

Epidermal growth factor receptor and glioblastoma multiforme: molecular basis for a new approach

Suppression of SRC Signaling Is Effective in Reducing Synergy between Glioblastoma and Stromal Cells

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