Altered CXCL12 expression reveals a dual role of CXCR4 in osteosarcoma primary tumor growth and metastasis

Neklyudova, Olga; Arlt, Matthias; Brennecke, Patrick; Thelen, Marcus; Gvozdenovic, Ana; Kuzmanov, Aleksandar; Robl, Bernhard; Botter, Sander M.; Born, Walter; Fuchs, Bruno

doi:10.1007/s00432-016-2185-5

Cited by 16 publications

(10 citation statements)

References 37 publications

(46 reference statements)

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“…Considering the similarity between molecular functions and cell components of hub IRGs, and through the ranking of semantic similarity, we discovered that CCR5, CXCL12 and CXCR4 are the most closely related genes. CCR5, CXCL12 and CXCR4 genes encode chemokine receptors or ligands, which plays a vital part role in the initiation and growth of OS 29 , 41 , 42 . These findings further support the reliability of our study.…”

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: 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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“…CXCR4 is the receptor of chemokine SDF-1, which regulates cell migration and involved in cancer progress and immunodeficiency disorder diseases [22, 23]. Recent study reported that CXCR4 was involved in metastatic potential in osteosarcoma at bone marrow and the lungs [24]. Previous studies showed that cancer cells have higher CXCR4 expression levels compared to normal cells [25, 26].…”

Section: Introductionmentioning

confidence: 99%

Effect of CXCR4 on Apoptosis in Osteosarcoma Cells via the PI3K/Akt/NF-κβ Signaling Pathway

Jiang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Osteosarcoma, the most common primary bone malignancy, arises from primitive transformed cells of mesenchymal origin with the worldwide increasing morbidity and mortality. Previous studies found apoptosis of osteosarcoma cells was essential for an effective manner to improve the progress of osteosarcoma, and CXCR4 has been demonstrated to be relevant with various tumor progress and metastasis. Methods: The proliferation of cells transfected with CXCR4 shRNA and control shRNA were measured by BrdU assay. Apoptosis was detected by flow cytometry. Apoptotic protein expression levels were detected by Western blot. Caspase activity was detected by Colorimetric Assay Kits using microplate reader. Activation of NF-κβ signaling after CXCR4 down-regulation in osteosarcoma cells was examined by constructing NF-κβ promoter luciferase reporter plasmid. The expression and activation of NF-κβ Signaling relevant protein were analyzed to investigate the relationship between Akt and NF-κβ signaling after the down-regulation of CXCR4 in osteosarcoma cells. Results: Down-regulation of CXCR4 significantly reduced the cell proliferation, while remarkably increased the cell apoptosis and apoptotic protein expression levels in osteosarcoma cells. Furthermore, down-regulation of CXCR4 induced cell apoptosis was caspase dependent in osteosarcoma cells. This study also showed CXCR4 down-regulation induced apoptosis through inhibiting PI3K/Akt/NF-κβ signaling pathway. In addition, endoplasmic reticulum stress (ERS) activation was involved in cell apoptosis induced down-regulation of CXCR4. Knockdown of partial ERS relevant proteins followed down-regulation of CXCR4 significantly inhibited cell apoptosis and the apoptotic protein expression levels. Conclusions: Taken together, the results demonstrated that down-regulation of CXCR4 could induce apoptosis of human osteosarcoma cells through inhibiting PI3K/Akt/NF-κβ signaling pathway, indicating that CXCR4 could be vital for the clinical therapy of osteosarcoma.

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“…There are always some cross-talks between different pathways in tumor occurrence and development, which provides a comprehensive understanding of tumor occurrence and development. Furthermore, the IL-8/CXCR1 axis and CXCL12/CXCR4/CXCR7 axis are commonly activated in the bone microenvironment when OS metastasis occur [ 29 , 31 , 33 , 39 , 53 ]. IL-8 and CXCL12, as the secreted molecules, are detected easily through peripheral blood.…”

Section: Discussionmentioning

confidence: 99%

“…Meanwhile, gene expression analysis showed that the focal adhesion, cytokine–cytokine receptor and extracellular matrix–receptor pathway significantly changed in MSCs compared to COS1NR cells [ 27 ]. The pathway molecules that dramatically altered were highly related to the tumor metastasis and angiogenesis such as the CXCL12/CXCR4 axis, MMP-2, and MMP-9 [ 27 , 28 , 29 ] ( Table 1 ). Some reports find that the interaction between MSCs and OS tumor cells is bidirectional ( Figure 1 ).…”

Section: Bone Microenvironment and Os Metastasismentioning

confidence: 99%

Bone Microenvironment and Osteosarcoma Metastasis

Yang

Tian

Zhao

et al. 2020

IJMS

176

156

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The bone microenvironment is an ideal fertile soil for both primary and secondary tumors to seed. The occurrence and development of osteosarcoma, as a primary bone tumor, is closely related to the bone microenvironment. Especially, the metastasis of osteosarcoma is the remaining challenge of therapy and poor prognosis. Increasing evidence focuses on the relationship between the bone microenvironment and osteosarcoma metastasis. Many elements exist in the bone microenvironment, such as acids, hypoxia, and chemokines, which have been verified to affect the progression and malignance of osteosarcoma through various signaling pathways. We thoroughly summarized all these regulators in the bone microenvironment and the transmission cascades, accordingly, attempting to furnish hints for inhibiting osteosarcoma metastasis via the amelioration of the bone microenvironment. In addition, analysis of the cross-talk between the bone microenvironment and osteosarcoma will help us to deeply understand the development of osteosarcoma. The cellular and molecular protagonists presented in the bone microenvironment promoting osteosarcoma metastasis will accelerate the exploration of novel therapeutic strategies towards osteosarcoma.

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Altered CXCL12 expression reveals a dual role of CXCR4 in osteosarcoma primary tumor growth and metastasis

Cited by 16 publications

References 37 publications

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

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

Effect of CXCR4 on Apoptosis in Osteosarcoma Cells via the PI3K/Akt/NF-κβ Signaling Pathway

Bone Microenvironment and Osteosarcoma Metastasis

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