Breast cancer metastasis to bone: From epithelial to mesenchymal transition to breast osteoblast-like cells

Scimeca, Manuel; Trivigno, Donata; Bonfiglio, Rita; Ciuffa, Sara; Urbano, Nicoletta; Schillaci, Orazio; Bonanno, Elena

doi:10.1016/j.semcancer.2020.01.004

Cited by 31 publications

(27 citation statements)

References 87 publications

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“…BC patients obtain only limited therapeutic outcomes, and most of them have poor improvements in survival benefits due to tumor recurrence and distant metastasis. [1][2][3][4][5] Multiple factors regulate the growth and metastasis of BC cells, such as EMT 27 as well as genetic and epigenetic alternations in tumor cells. 17,28,29 An increasing number of studies has focused on lncRNA dysregulation in tumor cells.…”

Section: Discussionmentioning

confidence: 99%

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<p>Long Non-Coding RNA NEAT1 Promotes the Proliferation, Migration, and Metastasis of Human Breast-Cancer Cells by Inhibiting miR-146b-5p Expression</p>

Hao

Yun

et al. 2020

CMAR

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Background: Breast cancer (BC) is the most commonly diagnosed cancer in women. Tumor recurrence and metastasis are the key causes of death in BC patients. Long noncoding RNA (lncRNA) is closely associated with BC progression. lncRNA nuclear-enriched abundant transcript (NEAT)1 has been reported to regulate the proliferation and mobility of several types of cancer cells. However, how lncRNA NEAT1 affects the proliferation and invasion of BC cells is not known. Methods: Quantitative real time-polymerase chain reaction (qRT-PCR) was used to measure expression of lncRNA NEAT1 and microRNA (miR)-146b-5p in BC tissues and cell lines. Cell Counting Kit (CCK)-8, cell colony-formation, wound-healing, and Transwell™ assays were undertaken to determine the effects of lncRNA NEAT1 and miR-146b-5p on progression of BC cells. The interaction between lncRNA NEAT1 and miR-146b-5p was examined by luciferase reporter, RNA-binding protein immunoprecipitation (RIP), and RNA-pulldown assays. Results: Expression of lncRNA NEAT1 was upregulated in BC tissues and cell lines. High expression of lncRNA NEAT1 predicted poor overall survival in BC patients. Silencing of expression of lncRNA NEAT1 inhibited epithelial-mesenchymal transition (EMT) and suppressed the proliferation, migration and invasion of BC cells. Ectopic expression of lncRNA NEAT1 induced EMT and promoted BC progression. Mechanistic investigations revealed that miR-146b-5p was a direct target of lncRNA NEAT1, and its expression was correlated negatively with expression of lncRNA NEAT1 in BC tissues. Conclusion: lncRNA NEAT1 could (i) serve as a novel prognostic marker for BC and (ii) be a potential therapeutic target for BC.

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Section: Discussionmentioning

confidence: 99%

“…1,2 However, most patients obtain only modest survival benefits and die from tumor recurrence and distant metastasis. [3][4][5] Therefore, understanding the mechanisms of the growth and metastasis of BC cells and identifying more efficacious therapeutic targets is extremely important.…”

Section: Introductionmentioning

confidence: 99%

<p>Long Non-Coding RNA NEAT1 Promotes the Proliferation, Migration, and Metastasis of Human Breast-Cancer Cells by Inhibiting miR-146b-5p Expression</p>

Hao

Yun

et al. 2020

CMAR

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“…Recently, the occurrence of the EMT phenomenon in the breast has been associated with the origin of BOLCs and the resulting formation of breast microcalcifications made of HA or Mg-HAp [12][13][14][15][16]. However, historically, EMT is considered a biological mechanism related to breast cancer development and metastasis formation [17,18].…”

Section: Discussionmentioning

confidence: 99%

“…As expected, both variants of BMP-2 were more expressed in the malignant lesions than the benign ones. Indeed, it is known that EMT, the presence of BOLCs, and breast microcalcifications made of HA or Mg-HAp are associated with breast cancer rather than benignant lesions [12][13][14][15][16]22].…”

Section: Discussionmentioning

confidence: 99%

BMP-2 Variants in Breast Epithelial to Mesenchymal Transition and Microcalcifications Origin

Scimeca

Giocondo

Montanaro

et al. 2020

Cells

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This study aims to investigate the possible different roles of the BMP-2 variants, cytoplasmic and nuclear variant, in both epithelial to mesenchymal transition and in microcalcifications origin in human breast cancers. To this end, the in situ expression of cytoplasmic and nuclear BMP-2 was associated with the expression of the main epithelial to mesenchymal transition biomarkers (e-cadherin and vimentin) and molecules involved in bone metabolisms (RUNX2, RANKL, SDF-1) by immunohistochemistry. In addition, the expression of cytoplasmic and nuclear BMP-2 was associated with the presence of microcalcifications. Our data showed a significant association among the number of cytoplasmic BMP-2-positive cells and the number of both vimentin (positive association) and e-cadherin (negative association) positive breast cells. Conversely, no associations were found concerning the nuclear BMP-2-positive breast cells. Surprisingly, the opposite result was obtained by analyzing the variants of BMP-2 and both the expression of RANKL and SDF-1 and the presence of microcalcifications. Specifically, the presence of microcalcifications was related to the expression of nuclear BMP-2 variant rather than the cytoplasmic one, as well as a strong association between the number of nuclear BMP-2 and the expression of the main breast osteoblast-like cells (BOLCs) biomarkers. To further corroborate these data, an in vitro experiment for demonstrating the co-expression of nBMP-2 and RANKL or vimentin or SDF-1 in breast cancer cells that acquire the capability to produce microcalcifications was developed. These investigations confirmed the association between the nBMP-2 expression and both RANKL and SDF-1. The data supports the idea that whilst cytoplasmic BMP-2 can be involved in epithelial to mesenchymal transition phenomenon, the nuclear variant is related to the essential mechanisms for the formation of breast microcalcifications. In conclusion, from these experimental and translational perspectives, the complexity of BMP-2 signaling will require a detailed understanding of the involvement of specific BMP-2 variants in breast cancers.

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“…Among patients with recurrent and metastatic advanced breast cancer, bone metastasis is the most common form of metastasis, with an incidence of 65-75%; patients with rst bone metastases account for 27-50% of cases [3]. Metastases commonly occur in the thoracolumbar vertebrae, sacrum, and ribs [4]. Patients with bone metastases from breast cancer often experience bone-related events such as bone pain, pathological fractures, vertebral compression or deformation, spinal cord compression, and hypercalcemia, which seriously affect patient quality of life [5].…”

Section: Introductionmentioning

confidence: 99%

Identification of key genes and long non-coding RNA related to bone metastasis in breast cancer by bioinformatics analysis

Huang

Yang

et al. 2020

Preprint

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BackgroundThe molecular mechanism of bone metastasis in breast cancer is largely unknown. We aimed to find key genes and long noncoding RNAs (lncRNAs) related to the bone metastasis of breast cancer using a bioinformatic approach. MethodsWe downloaded breast cancer bone metastasis gene expression data (GSE66206) and probe annotation files from the public database Gene Expression Omnibus. Then, we analyzed the network nodes to find core driver genes. Weighted correlation network analysis was performed on the gene expression profile of breast cancer bone metastasis to identify potential pathogenic modules. We performed function and pathway enrichment analyses of the genes and lncRNAs in the breast cancer bone metastasis-related modules. ResultsBased on our results, we constructed a differentially expressed lncRNA–mRNA network related to bone metastases in breast cancer and identified core driver genes, including BNIP3 and RP11-317-J19.1. ConclusionsOur findings provide a theoretical foundation for explaining the intrinsic molecular mechanism of breast cancer bone metastasis.

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Breast cancer metastasis to bone: From epithelial to mesenchymal transition to breast osteoblast-like cells

Cited by 31 publications

References 87 publications

<p>Long Non-Coding RNA NEAT1 Promotes the Proliferation, Migration, and Metastasis of Human Breast-Cancer Cells by Inhibiting miR-146b-5p Expression</p>

<p>Long Non-Coding RNA NEAT1 Promotes the Proliferation, Migration, and Metastasis of Human Breast-Cancer Cells by Inhibiting miR-146b-5p Expression</p>

BMP-2 Variants in Breast Epithelial to Mesenchymal Transition and Microcalcifications Origin

Identification of key genes and long non-coding RNA related to bone metastasis in breast cancer by bioinformatics analysis

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