Macrophage conditioned media promotes adipocyte cancer-association, which in turn stimulates breast cancer proliferation and migration

Abstract Background Breast cancer is the most common cancer in women and the leading cause of female cancer deaths worldwide. Obesity causes chronic inflammation and is a risk factor for post-menopausal breast cancer and poor prognosis. Obesity triggers increased infiltration of macrophages into adipose tissue, yet little research has focused on the effects of macrophages in early stages of breast tumor development in obese patients. In this study, the effects of pro-inflammatory macrophages on breast cancer-adipocyte crosstalk were investigated.Methods An innovative human cell co-culture system was used to model the paracrine interactions among adipocytes, macrophages, and breast cancer cells, and how they facilitate tumor progression. The effects on cancer cells were examined using cell counts and migration assays. Quantitative reverse-transcription polymerase chain reaction was used to measure the expression levels of several cytokines and proteases to analyze adipocyte cancer-association.Results Macrophage conditioned media intensified the effects of breast cancer-adipocyte crosstalk. Adipocytes became delipidated and increased production of pro-inflammatory cytokines, even in the absence of cancer cells, although the expression levels were highest with all three cell components. As a result, co-cultured breast cancer cells became more aggressive, with increased proliferation and migration compared to adipocyte-breast cancer co-cultures treated with unconditioned media.Conclusions Macrophage conditioned media promotes adipocyte cancer-association. These macrophage-adipocyte paracrine interactions promote breast cancer cell proliferation and migration. Thus, macrophages may contribute to adipocyte inflammation and cancer-association and promote breast cancer progression.

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Regulatory Mechanisms and Functional Roles of Hypoxia-Induced Long Non-Coding RNA MTORT1 in Breast Cancer Cells

Frontiers in Oncology ◽

10.3389/fonc.2021.663114 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yi-Chun Cheng ◽

Li-Yu Su ◽

Li-Han Chen ◽

Tzu-Pin Lu ◽

Eric Y. Chuang ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cancer Progression ◽

Breast Cancer Cells ◽

Breast Cancer Progression ◽

Luciferase Reporter ◽

Expression Levels ◽

Endogenous Expression ◽

And Migration ◽

Proliferation And Migration

Long non-coding RNAs (lncRNAs) have been found to participate in multiple genetic pathways in cancer. Also, mitochondria-associated lncRNAs have been discovered to modulate mitochondrial function and metabolism. Previously, we identified oxygen-responsive lncRNAs in MCF-7 breast cancer cells under different oxygen concentrations. Among them, a novel mitochondria-encoded lncRNA, mitochondrial oxygen-responsive transcript 1 (MTORT1), was chosen for further investigation. Nuclear, cytoplasmic, and mitochondrial fractionation assays were performed to evaluate the endogenous expression levels of MTORT1 in breast cancer cells. In vitro proliferation and migration assays were conducted to investigate the functions of MTORT1 in breast cancer cells by knockdown of MTORT1. RNA immunoprecipitation and luciferase reporter assays were used to examine the physical binding between MTORT1 and microRNAs. Our results showed that MTORT1 had low endogenous expression levels in breast cancer cells and was mainly located in the mitochondria. Knockdown of MTORT1 enhanced cell proliferation and migration, implying a tumor suppressor role of this novel mitochondrial lncRNA. MTORT1 served as sponge of miR-26a-5p to up-regulate its target genes, CREB1 and STK4. Our findings shed some light on the characterization, function, and regulatory mechanism of the novel hypoxia-induced mitochondrial lncRNA MTORT1, which functions as a microRNA sponge and may inhibit breast cancer progression. These data suggest that MTORT1 may be a candidate for therapeutic targeting of breast cancer progression.

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Interleukin enhancer-binding factor 3 and HOXC8 co-activate cadherin 11 transcription to promote breast cancer cells proliferation and migration

Oncotarget ◽

10.18632/oncotarget.22491 ◽

2017 ◽

Vol 8 (64) ◽

pp. 107477-107491 ◽

Cited By ~ 9

Author(s):

Yang Zhang ◽

Chenchen Yang ◽

Mingsheng Zhang ◽

Houli Liu ◽

Chen Gong ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Binding Factor ◽

And Migration ◽

Promote Breast Cancer ◽

Proliferation And Migration

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Hypoxia-Induced MALAT1 Promotes the Proliferation and Migration of Breast Cancer Cells by Sponging MiR-3064-5p

Frontiers in Oncology ◽

10.3389/fonc.2021.658151 ◽

2021 ◽

Vol 11 ◽

Author(s):

Chung-Hsien Shih ◽

Li-Ling Chuang ◽

Mong-Hsun Tsai ◽

Li-Han Chen ◽

Eric Y. Chuang ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Growth ◽

Cancer Cells ◽

Cancer Progression ◽

Breast Cancer Cells ◽

Cellular Migration ◽

Expression Levels ◽

Promote Tumor Growth ◽

Rna Immunoprecipitation ◽

And Migration

Hypoxia, a common process during tumor growth, can lead to tumor aggressiveness and is tightly associated with poor prognosis. Long noncoding RNAs (lncRNAs) are long ribonucleotides (>200 bases) with limited ability to translate proteins, and are known to affect many aspects of cellular function. One of their regulatory mechanisms is to function as a sponge for microRNA (miRNA) to modulate its biological functions. Previously, MALAT1 was identified as a hypoxia-induced lncRNA. However, the regulatory mechanism and functions of MALAT1 in breast cancer are still unclear. Therefore, we explored whether MALAT1 can regulate the functions of breast cancer cells through miRNAs. Our results showed the expression levels of MALAT1 were significantly up-regulated under hypoxia and regulated by HIF-1α and HIF-2α. Next, in contrast to previous reports, nuclear and cytoplasmic fractionation assays and fluorescence in situ hybridization indicated that MALAT1 was mainly located in the cytoplasm. Therefore, the labeling of MALAT1 as a nuclear marker should be done with the caveat. Furthermore, expression levels of miRNAs and RNA immunoprecipitation using antibody against AGO2 showed that MALAT1 functioned as a sponge of miRNA miR-3064-5p. Lastly, functional assays revealed that MALAT1 could promote cellular migration and proliferation of breast cancer cells. Our findings provide evidence that hypoxia-responsive long non-coding MALAT1 could be transcriptionally activated by HIF-1α and HIF-2α, act as a miRNA sponge of miR-3064-5p, and promote tumor growth and migration in breast cancer cells. These data suggest that MALAT1 may be a candidate for therapeutic targeting of breast cancer progression.

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M2 macrophages contribute to cell proliferation and migration of breast cancer

10.21203/rs.3.rs-39373/v1 ◽

2020 ◽

Author(s):

Daoyuan Tu ◽

Jin Dou ◽

Mingkao Wang ◽

Haiwen Zhuang ◽

Xiaoyu Xiaoyu

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cancer Progression ◽

Breast Cancer Cells ◽

M2 Macrophage ◽

M2 Macrophages ◽

Cell Proliferation And Migration ◽

And Migration ◽

Proliferation And Migration

Abstract Background: Breast cancer is a kind of malignant tumor that severely threatens women’s health and life worldwide. Macrophages have been reported to mediate tumor progression, while the potential mechanism still needs further identification.Methods: Human monocytic cell line THP-1 was used to induce M2-macrophage. Real-time PCR and western blot were performed to determine gene expression in mRNA and protein level, respectively. Cell proliferation was determined using MTT assays, while cell migration was detected based on the scratch wound healing assays.Results: The supernatant medium of M2-macrophages incubated breast cancer cells showed increased cell proliferation and reduced expression of IRF-7. Overexpression of IRF-7 reversed the increased level of M2-macrophage induced cell proliferation and migration. The supernatant medium of M2-macrophages incubation promoted miR-1587 expression in breast cancer cells. miR-1587 overexpression promoted cell proliferation and migration of breast cancer. In addition, miR-1587 knockdown suppressed cell proliferation and migration that induced by M2-macrophages. miR-1587 targets IRF-7 to regulate its expression. Knockdown of IRF-7 reversed the effects of miR-1587 knockdown on cell proliferation and migration.Conclusion: Collectively, this study revealed that miR-1587/IRF-7 mediated the mechanism of M2-macrophages-induced breast cancer progression, and this would shed light on the further clinical therapy of breast cancer.

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Macrophage conditioned media promotes adipocyte cancer-association, which in turn stimulates breast cancer proliferation and migration

10.21203/rs.3.rs-130272/v1 ◽

2020 ◽

Author(s):

Karin A. Vallega ◽

Dale B. Bosco ◽

Yi Ren ◽

Qing-Xiang Sang

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Conditioned Media ◽

Human Breast ◽

And Migration ◽

Proliferation And Migration

Abstract Background Breast cancer is the most common cancer in women and the leading cause of female cancer deaths worldwide. Obesity causes chronic inflammation and is a risk factor for post-menopausal breast cancer and poor prognosis. Obesity is known to trigger increased infiltration of macrophages into adipose tissue, yet little research has focused on the effects of macrophages in the early stages of breast tumor development in obese patients. In this study, the effects of pro-inflammatory macrophages on breast cancer-adipocyte crosstalk were investigated. Methods An innovative human cell co-culture system was used to model the paracrine interactions among adipocytes, macrophages, and breast cancer cells, and how they can facilitate tumor progression. The effects on human breast cancer cells were examined using cell counts and migration assays. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to measure the expression levels of several cytokines and proteases to analyze adipocyte cancer-association. Results Macrophage conditioned media intensified the effects of breast cancer-adipocyte crosstalk. More specifically, adipocytes became delipidated and increased production of pro-inflammatory cytokines, even in the absence of breast cancer cells, although the expression levels were highest with all three cell components. As a result, co-cultured breast cancer cells became more aggressive, with increased proliferation and migration potential when compared to adipocyte-breast cancer cell co-cultures treated with unconditioned media. Conclusions Macrophage conditioned media promotes adipocyte cancer-association and production of pro-inflammatory factors. These macrophage-adipocyte paracrine interactions promote human breast cancer cell proliferation and migration. Thus, macrophages may contribute to adipocyte inflammation and cancer-association and promote breast cancer progression.

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