S1PR1 as a Novel Promising Therapeutic Target in Cancer Therapy

Rostami, Narges; Nikkhoo, Afshin; Ajjoolabady, Amir; Azizi, Gholamreza; Hojjat‐Farsangi, Mohammad; Ghalamfarsa, Ghasem; Yousefi, Bahman; Yousefi, Mehdi; Jadidi‐Niaragh, Farhad

doi:10.1007/s40291-019-00401-5

Cited by 46 publications

(34 citation statements)

References 155 publications

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“…GP130, glycoprotein 130; IL-6, interleukin-6; mRNA, messenger RNA; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; NP, nanoparticles; SEM, standard error of the mean; S1PR1, sphingosine-1-phosphate receptor 1; siRNA, small interfering RNA; STAT3, signal transducer and activator of transcription 3 progressive effects stimulated by other cytokines of this family (Selander et al, 2004;Xu & Neamati, 2013). In addition, silencing these two surface receptors could inhibit activation of their other downstream signaling pathways, which play crucial roles in cancer progression (Rostami et al, 2019;Xu & Neamati, 2013).…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Coinhibition of S1PR1 and GP130 by siRNA‐loaded alginate‐conjugated trimethyl chitosan nanoparticles robustly blocks development of cancer cells

Rostami

Nikkhoo

Khazaei-Poul

et al. 2020

Journal Cellular Physiology

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There is an interconnected network between S1P/sphingosine‐1‐phosphate receptor 1 (S1PR1), IL‐6/glycoprotein 130 (GP130), and signal transducer and activator of transcription 3 (STAT3) signaling pathways in the tumor microenvironment, which leads to cancer progression. S1P/S1PR1 and IL‐6/GP130 signaling pathways phosphorylate and activate STAT3, and it then induces the expression of S1PR1 and interleukin‐6 (IL‐6) in a positive feedback loop leading to cancer progression. We hypothesized that blockade of this amplification loop can suppress the growth and development of cancer cells. Therefore, we silenced STAT3 upstream molecules including the S1PR1 and GP130 molecules in cancer cells using small interfering RNA (siRNA)‐loaded alginate‐conjugated trimethyl chitosan (ATMC) nanoparticles (NPs). The generated NPs had competent properties including the appropriate size, zeta potential, polydispersity index, morphology, high uptake of siRNA, high rate of capacity, high stability, and low toxicity. We evaluated the effects of siRNA loaded ATMC NPs on tumor hallmarks of three murine‐derived cancer cell lines, including 4T1 (breast cancer), B16‐F10 (melanoma), and CT26 (colon cancer). The results confirmed the tumor‐suppressive effects of combinational targeting of S1PR1 and GP130. Moreover, combination therapy could potently suppress tumor growth as assessed by the chick chorioallantoic membrane assay. In this study, we targeted this positive feedback loop for the first time and applied this novel combination therapy, which provides a promising approach for cancer treatment. The development of a potent nanocarrier system with ATMC for this combination was also another aspect of this study, which should be further investigated in cancer animal models in further studies.

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Section: Discussionmentioning

confidence: 99%

RETRACTED: Coinhibition of S1PR1 and GP130 by siRNA‐loaded alginate‐conjugated trimethyl chitosan nanoparticles robustly blocks development of cancer cells

Rostami

Nikkhoo

Khazaei-Poul

et al. 2020

Journal Cellular Physiology

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“…The coding product of the SIPR1 gene is a receptor protein that is similar to the G-protein-coupled receptor. When SIPR1 was combined with ligand S1P, the growth, invasion, and metastasis of lung cancer, ovarian cancer, and colon cancer are enhanced 38 – 40 . Hence, we can speculate that SIPR1 is pivotal in OS.…”

Section: Discussionmentioning

confidence: 99%

Development of a novel immune-related genes prognostic signature for osteosarcoma

Deng

Zhang

et al. 2020

Sci Rep

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Immune-related genes (IRGs) are responsible for osteosarcoma (OS) initiation and development. We aimed to develop an optimal IRGs-based signature to assess of OS prognosis. Sample gene expression profiles and clinical information were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Genotype-Tissue Expression (GTEx) databases. IRGs were obtained from the ImmPort database. R software was used to screen differentially expressed IRGs (DEIRGs) and functional correlation analysis. DEIRGs were analyzed by univariate Cox regression and iterative LASSO Cox regression analysis to develop an optimal prognostic signature, and the signature was further verified by independent cohort (GSE39055) and clinical correlation analysis. The analyses yielded 604 DEIRGs and 10 hub IRGs. A prognostic signature consisting of 13 IRGs was constructed, which strikingly correlated with OS overall survival and distant metastasis (p < 0.05, p < 0.01), and clinical subgroup showed that the signature’s prognostic ability was independent of clinicopathological factors. Univariate and multivariate Cox regression analyses also supported its prognostic value. In conclusion, we developed an IRGs signature that is a prognostic indicator in OS patients, and the signature might serve as potential prognostic indicator to identify outcome of OS and facilitate personalized management of the high-risk patients.

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Section: Sphingosine-1-phosphate (S1p)mentioning

confidence: 99%

“…Metastatic cancers have been shown to produce and secrete more S1P, as compared to primary tumors [ 91 ]. Such secreted S1P has been reported to be capable of establishing pre-metastatic niches in distant organs, such as the brain, through mechanisms involving S1PR1 [ 91 , 92 ]. Inhibition of S1P signaling using fingolimod in multiple myeloma revealed that metastasis to the bone marrow was due to the C-X-C chemokine receptor 4 (CXCR4)/C-X-C motif chemokine 12 (CXCL12) pathway [ 92 ].…”

Section: Sphingosine-1-phosphate (S1p)mentioning

confidence: 99%

Sphingolipid Metabolism in Glioblastoma and Metastatic Brain Tumors: A Review of Sphingomyelinases and Sphingosine-1-Phosphate

et al. 2020

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Glioblastoma (GBM) is a primary malignant brain tumor with a dismal prognosis, partially due to our inability to completely remove and kill all GBM cells. Rapid tumor recurrence contributes to a median survival of only 15 months with the current standard of care which includes maximal surgical resection, radiation, and temozolomide (TMZ), a blood–brain barrier (BBB) penetrant chemotherapy. Radiation and TMZ cause sphingomyelinases (SMase) to hydrolyze sphingomyelins to generate ceramides, which induce apoptosis. However, cells can evade apoptosis by converting ceramides to sphingosine-1-phosphate (S1P). S1P has been implicated in a wide range of cancers including GBM. Upregulation of S1P has been linked to the proliferation and invasion of GBM and other cancers that display a propensity for brain metastasis. To mediate their biological effects, SMases and S1P modulate signaling via phospholipase C (PLC) and phospholipase D (PLD). In addition, both SMase and S1P may alter the integrity of the BBB leading to infiltration of tumor-promoting immune populations. SMase activity has been associated with tumor evasion of the immune system, while S1P creates a gradient for trafficking of innate and adaptive immune cells. This review will explore the role of sphingolipid metabolism and pharmacological interventions in GBM and metastatic brain tumors with a focus on SMase and S1P.

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S1PR1 as a Novel Promising Therapeutic Target in Cancer Therapy

Cited by 46 publications

References 155 publications

RETRACTED: Coinhibition of S1PR1 and GP130 by siRNA‐loaded alginate‐conjugated trimethyl chitosan nanoparticles robustly blocks development of cancer cells

RETRACTED: Coinhibition of S1PR1 and GP130 by siRNA‐loaded alginate‐conjugated trimethyl chitosan nanoparticles robustly blocks development of cancer cells

Development of a novel immune-related genes prognostic signature for osteosarcoma

Sphingolipid Metabolism in Glioblastoma and Metastatic Brain Tumors: A Review of Sphingomyelinases and Sphingosine-1-Phosphate

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