CXCR7 maintains osteosarcoma invasion after CXCR4 suppression in bone marrow microenvironment

Wu, Chunhui; Wang, Jing; Liu, Na

doi:10.1177/1010428317701631

Cited by 9 publications

(7 citation statements)

References 37 publications

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“…They mentioned that CXCR7 was involved in modulating tumor microenvironment, tumor cell migration and apoptosis, thus revealing that these complex interactions provided insight into targeting CXCR7 as a potential anticancer therapy. Similar to our experimental observation in Figure 5, in (Han, 2017), suppressing CXCR4 was not enough to obstruct osteosarcoma invasion in bone marrow microenvironment, as CXCR7 was activated to sustain invasion. Therefore, they suggested that inhibiting both CXCR4 and CXCR7 could be a promising strategy in controlling osteosarcoma invasion, which perfectly matches our prediction and observation in LNCaP prostate cancer.…”

Section: Discussionsupporting

confidence: 86%

Disease mechanism, drug-target and biomarker prediction software: Application on prostate cancer and validation

Altay

Nurmemmedov

Kesari

et al. 2017

Preprint

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We introduce an R software package for condition-specific gene regulatory network analysis based on DC3NET algorithm. We also present an application of it on a real prostate dataset and demonstrate the benefit of the software. We performed genome-wide differential gene network analysis with the software on the LnCap androgen stimulated and deprived prostate cancer gene expression datasets (GSE18684) and inferred the androgen stimulated prostate cancer specific differential network. As an outstanding result, CXCR7 along with CXCR4 appeared to have the most important role in the androgen stimulated prostate specific genome-wide differential network. This blind estimation is strongly supported from the literature. The critical roles for CXCR4, a receptor over-expressed in many cancers, and CXCR7 on mediating tumor metastasis, along with their contributions as biomarkers of tumor behavior as well as potential therapeutic target were studied in several other types of cancers. In fact, a pharmaceutical company had already developed a therapy by inhibiting CXCR4 to block non-cancerous immuno-suppressive and pro-angiogenic cells from populating the tumor for disrupting the cancer environment and restoring normal immune surveillance functions. Considering this strong confirmation, our inferred regulatory network might reveal the driving mechanism of LnCap androgen stimulated prostate cancer. Because, CXCR4 appeared to be in the center of the largest subnetwork of our inferred differential network. Moreover, enrichment analyses for the largest subnetwork of it appeared to be significantly enriched in terms of axon guidance, fc gamma R-mediated phagocytosis and endocytosis. This also conforms with the recent literature in the field of prostate cancer.We demonstrate how to derive condition-specific gene targets from expression datasets on genome-wide level using differential gene network analysis. Our results showed that differential gene network analysis worked well in a prostate cancer dataset, which suggest the use of this approach as essential part of current expression data processing.Availability: The introduced R software package available in CRAN at https://cran.r-project.org/web/packages/dc3net and also at https://github.com/altayg/dc3net . CC-BY-NC 4.0 International license not peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was . http://dx.doi.org/10.1101/129742 doi: bioRxiv preprint first posted online Apr. 24, 2017; 2 BackgroundProstate cancer is the second most common cancer in the male population, with an estimated 417,000 new cases diagnosed each year in Europe (Ferlay, 2013). The activation of androgen receptor (AR) through androgens plays a crucial role in the development and progression of prostate cancer (Kaur, 2016; Anantharaman, 2015; Choudhary, 2011;Massie, 2011). For early detection of prostate cancer, prostate specific antigen (PSA) screening method has been used widely as a diagnostic tool (Karatas, 2015). However, PSA fails...

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Section: Discussionsupporting

confidence: 86%

Disease mechanism, drug-target and biomarker prediction software: Application on prostate cancer and validation

Altay

Nurmemmedov

Kesari

et al. 2017

Preprint

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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%

“…Clinicopathological analysis shows that CXCR4, receptor of CXCL12, and MMP-9 are overexpressed in OS with lung metastasis patients compared to the patients without metastasis [ 52 ]. CXCL12/CXCR4/CXCR7 was activated when a co-culture of bone marrow mesenchymal stem cells and OS cells ( Table 1 ) [ 53 ]. At the same time, the activation of CXCL12/CXCR4/CXCR7 in the co-culture model boosts the OS invasion [ 53 ].…”

Section: Bone Microenvironment and Os Metastasismentioning

confidence: 99%

“…CXCL12/CXCR4/CXCR7 was activated when a co-culture of bone marrow mesenchymal stem cells and OS cells ( Table 1 ) [ 53 ]. At the same time, the activation of CXCL12/CXCR4/CXCR7 in the co-culture model boosts the OS invasion [ 53 ]. Importantly, the CCL5/CCR5 axis not only enhances the migration of OS via αvβ3 but also facilitates tumor angiogenesis via PKC delta/c-Scr/HIF-1α pathway [ 54 ] ( Table 1 ).…”

Section: Bone Microenvironment and Os Metastasismentioning

confidence: 99%

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Bone Microenvironment and Osteosarcoma Metastasis

Yang

Tian

Zhao

et al. 2020

IJMS

187

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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“…Human Mesenchymal Stem Cells (hMSCs) play also a major role in the communication between tumor cells and their microenvironment, as highlighted by recent studies, including increased proliferation and migration of tumor cells. On one hand, bone marrow MSCs promote migration and invasion through direct secretion of several cytokines such as C-X-C motif chemokine ligand 12 (CXCL12) that binds to C-X-C motif chemokine receptor 4 (CXCR4) or CXCR7 on osteosarcoma associated with lower overall patient survival [26,27,28]. Interleukin-6, secreted by MSCs, contributes to promote metastatic dissemination of osteosarcoma [29,30].…”

Section: Tumor Microenvironment: Crucial Role In Bone Sarcoma Tumomentioning

confidence: 99%

New Insights about the Wnt/β-Catenin Signaling Pathway in Primary Bone Tumors and Their Microenvironment: A Promising Target to Develop Therapeutic Strategies?

Danieau

Morice

Rédini

et al. 2019

IJMS

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Osteosarcoma and Ewing sarcoma are the most common malignant primary bone tumors mainly occurring in children, adolescents and young adults. Current standard therapy includes multidrug chemotherapy and/or radiation specifically for Ewing sarcoma, associated with tumor resection. However, patient survival has not evolved for the past decade and remains closely related to the response of tumor cells to chemotherapy, reaching around 75% at 5 years for patients with localized forms of osteosarcoma or Ewing sarcoma but less than 30% in metastatic diseases and patients resistant to initial chemotherapy. Despite Ewing sarcoma being characterized by specific EWSR1-ETS gene fusions resulting in oncogenic transcription factors, currently, no targeted therapy could be implemented. It seems even more difficult to develop a targeted therapeutic strategy in osteosarcoma which is characterized by high complexity and heterogeneity in genomic alterations. Nevertheless, the common point between these different bone tumors is their ability to deregulate bone homeostasis and remodeling and divert them to their benefit. Therefore, targeting different actors of the bone tumor microenvironment has been hypothesized to develop new therapeutic strategies. In this context, it is well known that the Wnt/β-catenin signaling pathway plays a key role in cancer development, including osteosarcoma and Ewing sarcoma as well as in bone remodeling. Moreover, recent studies highlight the implication of the Wnt/β-catenin pathway in angiogenesis and immuno-surveillance, two key mechanisms involved in metastatic dissemination. This review focuses on the role played by this signaling pathway in the development of primary bone tumors and the modulation of their specific microenvironment.

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CXCR7 maintains osteosarcoma invasion after CXCR4 suppression in bone marrow microenvironment

Cited by 9 publications

References 37 publications

Disease mechanism, drug-target and biomarker prediction software: Application on prostate cancer and validation

Disease mechanism, drug-target and biomarker prediction software: Application on prostate cancer and validation

Bone Microenvironment and Osteosarcoma Metastasis

New Insights about the Wnt/β-Catenin Signaling Pathway in Primary Bone Tumors and Their Microenvironment: A Promising Target to Develop Therapeutic Strategies?

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