CXCR4 Accelerates Osteoclastogenesis Induced by Non-Small Cell Lung Carcinoma Cells Through Self-Potentiation and VCAM1 Secretion

Liao, Tongquan; Chen, Wugui; Sun, Jing; Zhang, Ying; Hu, Xu; Yang, Sizhen; Qiu, Hao; Li, Songtao; Chu, Tongwei

doi:10.1159/000494533

Cited by 10 publications

(10 citation statements)

References 36 publications

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“…Thus, research on mechanisms about how NSCLC bone metastases occur has been a hot spot in recent years. LncRNA MALAT1, miRNA-33, CXCR4, and TGF-β signaling have all been reported to contribute to bone metastases of NSCLC (Liu et al, 2016;Popper, 2016;Liao et al, 2018;Yang et al, 2019). Interestingly, in our present work, we firstly report that PNMA5 enhances NSCLC bone metastases as a target gene of BMP2 signaling.…”

Section: Discussionsupporting

confidence: 44%

“…The gene expression changes of NSCLC cells can mediate the secreting factors of NSCLC cells, which subsequently regulate the osteoclast differentiation. High expression of CXCR4 in NSCLC cells have been shown to promote cancer cells-mediated osteoclast differentiation through secreting VCAM1 (Liao et al, 2018). Moreover, C5aR1 can also enhance NSCLC cells to induce osteoclast differentiation through secreting CXCL16 (Ajona et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

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PNMA5 Promotes Bone Metastasis of Non-small-Cell Lung Cancer as a Target of BMP2 Signaling

Huang

Yun

Wang

et al. 2021

Front. Cell Dev. Biol.

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Bone metastases frequently occur in NSCLC patients at the late stage, indicating poor survival. However, mechanisms about the initiation of NSCLC bone metastases remain largely unclear. In our previous reports, BMP2 signaling activation has been found to enhance NSCLC bone metastases through enhancing carcinoma cells migration, invasion, osteoclasts differentiation and osteoblasts immature differentiation. Nevertheless, downstream target genes of BMP2 contributing to those processes still remain unknown. In this project, we find that the expression of Pnma5 is higher in metastatic bone tumors of Lewis lung carcinoma than in metastatic lung tumors and parental Lewis lung cells. Pnma5 overexpression not only can promote cell migration and invasion of NSCLC cells but also tumor-induced osteoclasts differentiation. Interestingly, knockdown of Pnma5 in Lewis lung cells blocks BMP2 signaling from inducing Lewis lung cells migration and invasion. Although BMP2 signaling can promote Lewis lung cells-induced osteoclasts differentiation from macrophages, this effect can also be blocked when Pnma5 is knocked down in Lewis lung cells. Moreover, Pnma5 can promote NSCLC bone metastases in vivo as the downstream target of BMP2. Those results above indicate that BMP2 signaling enhances NSCLC bone metastases via its direct downstream target gene Pnma5. This research reveals the detailed molecular mechanism about how BMP2 signaling contributes to NSCLC bone metastases via PNMA5 and provides a new potential therapeutic target for the treatment of NSCLC bone metastases.

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Section: Discussionsupporting

confidence: 44%

Section: Discussionmentioning

confidence: 99%

PNMA5 Promotes Bone Metastasis of Non-small-Cell Lung Cancer as a Target of BMP2 Signaling

Huang

Yun

Wang

et al. 2021

Front. Cell Dev. Biol.

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“…Mechanistically, the NSCLC-derived exosomes produce amphiregulin which induces EGFR pathway activation in pre-osteoclasts, consequently causing increased expression of receptor activator of nuclear factor-kappa-Β ligand (RANKL), associated with the vicious cycle in osteolytic bone metastasis [ 74 ]. Lung tumor-derived exosomal induction of osteoclastogenesis is also linked with factors such as acceleration by C-X-C chemokine receptor type 4 (CXCR4) through self-potentiation and vascular cell adhesion molecule 1 (VCAM1) secretion [ 75 ], differential expression of the RANKL/RANK/OPG system [ 76 ], and activation of the EGF pathway by multiple myeloma-derived exosomes enriched in amphiregulin in the bone microenvironment [ 77 ]. Sequencing of plasma-derived exosomal miRNAs of lung cancer patients revealed three consensus clusters that showed significant differential expression.…”

Section: Exosomes and Lung Cancer Metastasismentioning

confidence: 99%

The role of exosomes in lung cancer metastasis and clinical applications: an updated review

et al. 2021

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Lung cancer is the leading cause of cancer-associated deaths accounting for 24% of all cancer deaths. As a crucial phase of tumor progression, lung cancer metastasis is linked to over 70% of these mortalities. In recent years, exosomes have received increasing research attention in their role in the induction of carcinogenesis and metastasis in the lung. In this review, recent studies on the contribution of exosomes to lung cancer metastasis are discussed, particularly highlighting the role of lung tumor-derived exosomes in immune system evasion, epithelial-mesenchymal transition, and angiogenesis, and their involvement at both the pre-metastatic and metastatic phases. The clinical application of exosomes as therapeutic drug carriers, their role in antitumor drug resistance, and their utility as predictive biomarkers in diagnosis and prognosis are also presented. The metastatic activity, a complex multistep process of cancer cell invasion, survival in blood vessels, attachment and subsequent colonization of the host's organs, is integrated with exosomal effects. Exosomes act as functional mediating factors in cell–cell communication, influencing various steps of the metastatic cascade. To this end, lung cancer cell-derived exosomes enhance cell proliferation, angiogenesis, and metastasis, regulate drug resistance, and antitumor immune activities during lung carcinogenesis, and are currently being explored as an important component in liquid biopsy assessment for diagnosing lung cancer. These nano-sized extracellular vesicles are also being explored as delivery vehicles for therapeutic molecules owing to their unique properties of biocompatibility, circulatory stability, decreased toxicity, and tumor specificity. The current knowledge of the role of exosomes highlights an array of exosome-dependent pathways and cargoes that are ripe for exploiting therapeutic targets to treat lung cancer metastasis, and for predictive value assessment in diagnosis, prognosis, and anti-tumor drug resistance.

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“…In addition, it was marginally correlated with brain metastasis (p=0.068) and lymph node metastasis (p=0.085), as well as worse OS (p=0.004) and PFS (p=0.005). Liao et al (122) Tumor tissue…”

Section: C-mesenchymal-epithelial Transitionmentioning

confidence: 99%

“…Recent findings indicated that CXCR4 expression on tumor cells plays a positive role in key downstream pathways, including PI3K/AKT/mechanistic target of rapamycin kinase (PI3K/AKT/MTOR) and extracellular signal-regulated kinase 1/2 (ERK1/2), which promote tumor proliferation and migration (149). Vascular cell adhesion molecule 1 (VCAM1) was also shown to be an activator of CXCR4, with ADAM metallopeptidase domain 17 (ADAM17) as a downstream mediator (122). Zuo et al (150) demonstrated that overexpression of CXCR4 enhanced cell motility and invasion via EGFR and matrix metallopeptidase 9 (MMP9), owing to the positive correlation among them.…”

Section: C5a (Cd88)/ C5armentioning

confidence: 99%

Predictive and Prognostic Biomarkers for Lung Cancer Bone Metastasis and Their Therapeutic Value

et al. 2021

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Lung cancer is the leading cause of cancer-related death worldwide. Bone metastasis, which usually accompanies severe skeletal-related events, is the most common site for tumor distant dissemination and detected in more than one-third of patients with advanced lung cancer. Biopsy and imaging play critical roles in the diagnosis of bone metastasis; however, these approaches are characterized by evident limitations. Recently, studies regarding potential biomarkers in the serum, urine, and tumor tissue, were performed to predict the bone metastases and prognosis in patients with lung cancer. In this review, we summarize the findings of recent clinical research studies on biomarkers detected in samples obtained from patients with lung cancer bone metastasis. These markers include the following: (1) bone resorption-associated markers, such as N-terminal telopeptide (NTx)/C-terminal telopeptide (CTx), C-terminal telopeptide of type I collagen (CTx-I), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), pyridinoline (PYD), and parathyroid hormone related peptide (PTHrP); (2) bone formation-associated markers, including total serum alkaline phosphatase (ALP)/bone specific alkaline phosphatase(BAP), osteopontin (OP), osteocalcin (OS), amino-terminal extension propeptide of type I procollagen/carboxy-terminal extension propeptide of type I procollagen (PICP/PINP); (3) signaling markers, including epidermal growth factor receptor/Kirsten rat sarcoma/anaplastic lymphoma kinase (EGFR/KRAS/ALK), receptor activator of nuclear factor κB ligand/receptor activator of nuclear factor κB/osteoprotegerin (RANKL/RANK/OPG), C-X-C motif chemokine ligand 12/C-X-C motif chemokine receptor 4 (CXCL12/CXCR4), complement component 5a receptor (C5AR); and (4) other potential markers, such as calcium sensing receptor (CASR), bone sialoprotein (BSP), bone morphogenetic protein 2 (BMP2), cytokeratin 19 fragment/carcinoembryonic antigen (CYFRA/CEA), tissue factor, cell-free DNA, long non-coding RNA, and microRNA. The prognostic value of these markers is also investigated. Furthermore, we listed some clinical trials targeting hotspot biomarkers in advanced lung cancer referring for their therapeutic effects.

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CXCR4 Accelerates Osteoclastogenesis Induced by Non-Small Cell Lung Carcinoma Cells Through Self-Potentiation and VCAM1 Secretion

Cited by 10 publications

References 36 publications

PNMA5 Promotes Bone Metastasis of Non-small-Cell Lung Cancer as a Target of BMP2 Signaling

PNMA5 Promotes Bone Metastasis of Non-small-Cell Lung Cancer as a Target of BMP2 Signaling

The role of exosomes in lung cancer metastasis and clinical applications: an updated review

Predictive and Prognostic Biomarkers for Lung Cancer Bone Metastasis and Their Therapeutic Value

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