Differential expression of CXCR4 and CXCR7 with various stem cell markers in paired human primary and recurrent glioblastomas

Flüh, Charlotte; Hattermann, Kirsten; Mehdorn, H. Maximilian; Synowitz, Michael; Held‐Feindt, Janka

doi:10.3892/ijo.2016.3354

Cited by 15 publications

(12 citation statements)

References 41 publications

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“…It has been reported that CXCR4 is overexpressed in many tumor cells, including glioma, colorectal, breast, lung, prostate and cervical cancer (2–4). Consistently, high expression of CXCR4 was observed in highly invasive glioma stem cells (5). SDF-1α promotes tumor growth in a paracrine fashion by directly stimulating tumor cell proliferation and survival via CXCR4.…”

Section: Introductionmentioning

confidence: 56%

N-terminal polypeptide derived from vMIP-II exerts its antitumor activity by inhibiting the CXCR4 pathway in human glioma

Yang

Wang

et al. 2017

International Journal of Oncology

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Emerging evidence demonstrates that the stromal derived factor-1 (SDF-1α)/CXCR4 axis is associated with tumor aggressiveness and metastasis, including glioma, the most common brain cancer. In the present study, we demonstrated that a novel designed peptide NT21MP of viral macrophage inflammatory protein II, targeting CXCR4 inhibits SDF-1α-induced activation in glioma. The effects of NT21MP on CXCR4 expression, cell survival and migration were assessed on the human glioma cell line U251 and SHG-44 exposed to SDF-1α, by western blotting, MTT assay, flow cytometry and Transwell migration assay. Our results illustrated that NT21MP inhibited SDF-1α induced proliferation, migration and invasion by upregulated pro-apoptotic genes (Bak1 and caspase-3) and downregulated Bcl-2/Bax as well as cell cycle regulators (cyclin D1 and CDK4) to arrest cell cycle in G0/G1 phase and promote apoptosis. By RT-qPCR and immunofluorescence we found that CXCR4 was highly expressed in SHG-44 cells. Our results from wound healing and Transwell invasion assays indicated silencing of CXCR4 significantly inhibited the SDF-1α-induced migration and invasion; similarly, flow cytometry showed that treatment with si-CXCR4 affected cell cycle and induced cell apoptosis in SHG-44. However, these effects were significantly weakened by NT21MP. In conclusion, the present study indicates that NT21MP plays a regulatory role in the SDF-1α/CXCR4 axis and further manages the invasion, migration, apoptosis and cell cycle of glioma cells. Thus, NT21MP might represent a novel therapeutic approach against glioma.

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Section: Introductionmentioning

confidence: 56%

N-terminal polypeptide derived from vMIP-II exerts its antitumor activity by inhibiting the CXCR4 pathway in human glioma

Yang

Wang

et al. 2017

International Journal of Oncology

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“…These properties suggest that CXCR4 antagonists may help control this disease. CXCR4 expression varies significantly among different subtypes of GBM and in glioblastoma stem‐like cells (GSCs) 188–192 . Low expression of CXCR4 due to processes such as promoter hypermethylation might predict favorable overall survival.…”

Section: Cxcr4 In Cancer Development and Progression: Tumor Examplesmentioning

confidence: 99%

At the Bench: Pre-clinical evidence for multiple functions of CXCR4 in cancer

Luker

Yang

Richmond

et al. 2020

Journal of Leukocyte Biology

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Signaling through chemokine receptor, C-X-C chemokine receptor type 4 (CXCR4) regulates essential processes in normal physiology, including embryogenesis, tissue repair, angiogenesis, and trafficking of immune cells. Tumors co-opt many of these fundamental processes to directly stimulate proliferation, invasion, and metastasis of cancer cells. CXCR4 signaling contributes to critical functions of stromal cells in cancer, including angiogenesis and multiple cell types in the tumor immune environment. Studies in animal models of several different types of cancers consistently demonstrate essential functions of CXCR4 in tumor initiation, local invasion, and metastasis to lymph nodes and distant organs. Data from animal models support clinical observations showing that integrated effects of CXCR4 on cancer and stromal cells correlate with metastasis and overall poor prognosis in >20 different human malignancies. Small molecules, Abs, and peptidic agents have shown anticancer efficacy in animal models, sparking ongoing efforts at clinical translation for cancer therapy. Investigators also are developing companion CXCR4-targeted imaging agents with potential to stratify patients for CXCR4-targeted therapy and monitor treatment efficacy. Here, pre-clinical studies demonstrating functions of CXCR4 in cancer are reviewed.

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“…Nanog is expressed in various kinds of human tumors, including glioblastoma ( Figure 3 a), the most common malignant primary brain tumors [ 18 , 46 , 47 ]. On the other hand, CXCR4 controls the migration of neuronal cells [ 48 , 49 ], and it is the most common chemokine receptor expressed by many cancer cells, including glioblastoma [ 36 , 50 ], where CXCR4 plays a role in cancer cell migration [ 51 ]. To find out if h-NANOG can regulate CXCR4 expression in human cancer cells, we studied how changes in h-NANOG level affected the expression of CXCR4 in human glioblastoma and astrocytoma cell lines.…”

Section: Resultsmentioning

confidence: 99%

The Embryonic Key Pluripotent Factor NANOG Mediates Glioblastoma Cell Migration via the SDF1/CXCR4 Pathway

Sanchez‐Sanchez¹,

Garcı́a-España

Sánchez-Gómez

et al. 2021

IJMS

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NANOG is a key transcription factor required for maintaining pluripotency of embryonic stem cells. Elevated NANOG expression levels have been reported in many types of human cancers, including lung, oral, prostate, stomach, breast, and brain. Several studies reported the correlation between NANOG expression and tumor metastasis, revealing itself as a powerful biomarker of poor prognosis. However, how NANOG regulates tumor progression is still not known. We previously showed in medaka fish that Nanog regulates primordial germ cell migration through Cxcr4b, a chemokine receptor known for its ability to promote migration and metastasis in human cancers. Therefore, we investigated the role of human NANOG in CXCR4-mediated cancer cell migration. Of note, we found that NANOG regulatory elements in the CXCR4 promoter are functionally conserved in medaka fish and humans, suggesting an evolutionary conserved regulatory axis. Moreover, CXCR4 expression requires NANOG in human glioblastoma cells. In addition, transwell assays demonstrated that NANOG regulates cancer cell migration through the SDF1/CXCR4 pathway. Altogether, our results uncover NANOG-CXCR4 as a novel pathway controlling cellular migration and support Nanog as a potential therapeutic target in the treatment of Nanog-dependent tumor progression.

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Differential expression of CXCR4 and CXCR7 with various stem cell markers in paired human primary and recurrent glioblastomas

Cited by 15 publications

References 41 publications

N-terminal polypeptide derived from vMIP-II exerts its antitumor activity by inhibiting the CXCR4 pathway in human glioma

N-terminal polypeptide derived from vMIP-II exerts its antitumor activity by inhibiting the CXCR4 pathway in human glioma

At the Bench: Pre-clinical evidence for multiple functions of CXCR4 in cancer

The Embryonic Key Pluripotent Factor NANOG Mediates Glioblastoma Cell Migration via the SDF1/CXCR4 Pathway

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