scholarly journals Precision health for breast cancer metastasis: biomaterial scaffolds as an engineered metastatic niche to define, study, and monitor metastatic progression

Oncoscience ◽  
2019 ◽  
Vol 6 (11-12) ◽  
pp. 380-382 ◽  
Author(s):  
Grace G. Bushnell ◽  
Max S. Wicha ◽  
Jacqueline S. Jeruss ◽  
Lonnie D. Shea
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Metastatic Progression ◽  
Metastatic Niche ◽  
Biomaterial Scaffolds ◽  
Precision Health

Priming the ‘Soil’ for Breast Cancer Metastasis: The Pre-Metastatic Niche

2007 ◽  
Vol 26 (1) ◽  
pp. 65-74 ◽  
Author(s):  
Bethan Psaila ◽  
Rosandra N. Kaplan ◽  
Elisa R. Port ◽  
David Lyden
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Metastatic Niche

scholarly journals Tiny miRNAs Play a Big Role in the Treatment of Breast Cancer Metastasis

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 337
Author(s):  
Andrea York Tiang Teo ◽  
Xiaoqiang Xiang ◽  
Minh TN Le ◽  
Andrea Li-Ann Wong ◽  
Qi Zeng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Tumour Progression ◽  
Tumour Microenvironment ◽  
Breast Cancer Metastasis ◽  
Metastatic Progression ◽  
Mesenchymal Transition ◽  
Recent Developments ◽  
Underlying Mechanisms

Distant organ metastases accounts for the majority of breast cancer deaths. Given the prevalence of breast cancer in women, it is imperative to understand the underlying mechanisms of its metastatic progression and identify potential targets for therapy. Since their discovery in 1993, microRNAs (miRNAs) have emerged as important regulators of tumour progression and metastasis in various cancers, playing either oncogenic or tumour suppressor roles. In the following review, we discuss the roles of miRNAs that potentiate four key areas of breast cancer metastasis—angiogenesis, epithelial-mesenchymal transition, the Warburg effect and the tumour microenvironment. We then evaluate the recent developments in miRNA-based therapies in breast cancer, which have shown substantial promise in controlling tumour progression and metastasis. Yet, certain challenges must be overcome before these strategies can be implemented in clinical trials.

scholarly journals Polyphenol-Rich Muscadine Grape Extract Reduces Triple Negative Breast Cancer Metastasis in Mice with Changes in the Gut Microbiome

2021 ◽  
Author(s):  
Marianne Collard ◽  
Nataleigh N Austin ◽  
Heather Brown-Harding ◽  
Brian Westwood ◽  
E Ann Tallant ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Cancer Metastasis ◽  
Triple Negative ◽  
Breast Cancer Metastasis ◽  
Metastatic Progression ◽  
Microbial Composition ◽  
Cytoskeletal Organization ◽  
Grape Extract ◽  
Muscadine Grape

Abstract Background Triple negative breast cancer (TNBC) has a high propensity to metastasize and no treatments are available to slow or prevent metastatic progression. The goal of this study is to determine whether a proprietary high-polyphenol content muscadine grape extract (MGE) inhibits TNBC metastasis. Methods 4T1 TNBC cells were injected into the mammary fat pad of 6-week-old female Balb/c mice. After 2 weeks, tumors were surgically removed and mice were placed into a control (n=8) or treatment group that received 0.1 mg/mL total phenolics MGE in the drinking water (n=8) for 4 weeks. Immunohistochemistry (Ki67, α-SMA) and hemotoxylin and eosin staining were used to quantify metastases. Gut microbial composition was determined by 16S rRNA sequencing and short chain fatty acids (SCFAs) were detected by gas chromatography. MDA-MB-231, BT-549 and 4T1 TNBC cell motility and cytoskeletal organization was assessed in vitr o by scratch wound migration and confocal microscopy, respectively. Data were evaluated by student’s t -test. Results MGE reduced metastatic proliferation in mouse lungs (33.3%) and livers (58.3%) and decreased the number (51.1%) and size (17.4%) of liver metastases, resulting in a 55.7% reduction in metastatic tumor burden ( P < 0.01). Serum IL-6 was reduced 99.6% in MGE-treated mice ( P = 0.06). MGE attenuated migration, altered cytoskeletal organization, and reduced RHAMM expression in TNBC cells ( P < 0.05). The gut microbiota, a mediator of polyphenolic bioactivities, was altered significantly in MGE-treated mice; MGE increased the alpha diversity (7.14%), Firmicutes/Bacteroidetes ratio (2-fold), relative abundance of butyrate-producing genera, and butyrate (3-fold) ( P < 0.05). Butyrate inhibited 4T1 cell proliferation and migration, suggesting butyrate contributes to MGE’s anti-metastatic activities ( P < 0.05). Conclusion Our results indicate that MGE may be an effective adjuvant therapy to reduce TNBC metastatic progression.

scholarly journals Targeted inactivation of β1 integrin induces β3 integrin switching, which drives breast cancer metastasis by TGF-β

2013 ◽  
Vol 24 (21) ◽  
pp. 3449-3459 ◽  
Author(s):  
Jenny G. Parvani ◽  
Amy J. Galliher-Beckley ◽  
Barbara J. Schiemann ◽  
William P. Schiemann
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Breast Cancer Metastasis ◽  
Β1 Integrin ◽  
Metastatic Progression ◽  
Breast Cancer Patients ◽  
Mesenchymal Transition ◽  
Β3 Integrin

Mammary tumorigenesis and epithelial–mesenchymal transition (EMT) programs cooperate in converting transforming growth factor-β (TGF-β) from a suppressor to a promoter of breast cancer metastasis. Although previous reports associated β1 and β3 integrins with TGF-β stimulation of EMT and metastasis, the functional interplay and plasticity exhibited by these adhesion molecules in shaping the oncogenic activities of TGF-β remain unknown. We demonstrate that inactivation of β1 integrin impairs TGF-β from stimulating the motility of normal and malignant mammary epithelial cells (MECs) and elicits robust compensatory expression of β3 integrin solely in malignant MECs, but not in their normal counterparts. Compensatory β3 integrin expression also 1) enhances the growth of malignant MECs in rigid and compliant three-dimensional organotypic cultures and 2) restores the induction of the EMT phenotypes by TGF-β. Of importance, compensatory expression of β3 integrin rescues the growth and pulmonary metastasis of β1 integrin–deficient 4T1 tumors in mice, a process that is prevented by genetic depletion or functional inactivation of β3 integrin. Collectively our findings demonstrate that inactivation of β1 integrin elicits metastatic progression via a β3 integrin–specific mechanism, indicating that dual β1 and β3 integrin targeting is necessary to alleviate metastatic disease in breast cancer patients.

scholarly journals Low lamin A levels enhance confined cell migration and metastatic capacity in breast cancer

2021 ◽  
Author(s):  
Emily S Bell ◽  
Pragya Shah ◽  
Noam Zuela - Sopilniak ◽  
Dongsung Kim ◽  
Alexandra L McGregor ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Disease Free Survival ◽  
Breast Cancer Metastasis ◽  
Lamin A ◽  
Metastatic Progression ◽  
Altered Expression

Aberrations in nuclear size and shape are commonly used to identify cancerous tissue. However, it remains unclear whether the disturbed nuclear structure directly contributes to the cancer pathology or is merely a consequence of other events occurring during tumorigenesis. Here, we show that highly invasive and proliferative breast cancer cells have lower expression of the nuclear envelope proteins lamin A/C, leading to increased nuclear deformability that permits enhanced cell migration through confined environments that mimic interstitial spaces encountered during metastasis. Importantly, increasing lamin A/C expression in highly invasive breast cancer cells altered expression of numerous other proteins implicated in metastatic progression. Further supporting an important role of lamins in breast cancer metastasis, analysis of lamin levels in human breast tumors revealed a significant association between lower lamin A levels and decreased disease-free survival. These findings suggest that downregulation of lamin A/C may influence both biochemical and physical properties of the cell to promote breast cancer metastatic progression.

The influence of the pre-metastatic niche on breast cancer metastasis

2016 ◽  
Vol 380 (1) ◽  
pp. 281-288 ◽  
Author(s):  
Josie Ursini-Siegel ◽  
Peter M. Siegel
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Metastatic Niche

scholarly journals EGFL9 promotes breast cancer metastasis by inducing cMET activation and metabolic reprogramming

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Fanyan Meng ◽  
Ling Wu ◽  
Lun Dong ◽  
Allison V. Mitchell ◽  
C. James Block ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Cell Metabolism ◽  
Breast Cancer Metastasis ◽  
Metabolic Reprogramming ◽  
Metabolic Phenotype ◽  
Migration And Invasion ◽  
Metastatic Progression ◽  
Basal Like Breast Cancer

Abstract The molecular mechanisms driving metastatic progression in triple-negative breast cancer (TNBC) patients are poorly understood. In this study, we demonstrate that epidermal growth factor-like 9 (EGFL9) is significantly upregulated in basal-like breast cancer cells and associated with metastatic progression in breast tumor samples. Functionally, EGFL9 is both necessary and sufficient to enhance cancer cell migration and invasion, as well as distant metastasis. Mechanistically, we demonstrate that EGFL9 binds cMET, activating cMET-mediated downstream signaling. EGFL9 and cMET co-localize at both the cell membrane and within the mitochondria. We further identify an interaction between EGFL9 and the cytochrome c oxidase (COX) assembly factor COA3. Consequently, EGFL9 regulates COX activity and modulates cell metabolism, promoting a Warburg-like metabolic phenotype. Finally, we show that combined pharmacological inhibition of cMET and glycolysis reverses EGFL9-driven stemness. Our results identify EGFL9 as a therapeutic target for combating metastatic progression in TNBC.

scholarly journals HSD11β1 promotes EMT-mediated breast cancer metastasis

2021 ◽  
Author(s):  
Joji Nakayama ◽  
Takamasa Ishikawa ◽  
Tatsunori Nishimura ◽  
Sanae Yamanaka ◽  
Noriko Gotoh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Hormone Receptors ◽  
Metastatic Breast ◽  
Breast Cancer Metastasis ◽  
Steroid Hormone Receptors ◽  
Metastatic Progression ◽  
Mesenchymal Transition

AbstractAbnormal biosyntheses of steroid hormones and dysregulation of steroid hormone receptors contribute to breast cancer metastasis but the mechanisms of that are poorly understand. Here we report a stress hormone producing enzyme, Hydroxysteroid (11-Beta) Dehydrogenase 1 (HSD11β1) promotes breast cancer metastasis. HSD11β1 was ectopically expressed in seventy-one percent of triple-negative breast tumors and correlated with shorter overall survival. HSD11β1 significantly promoted breast cancer metastasis through induction of epithelial-to-mesenchymal transition (EMT); conversely, pharmacologic and genetic inhibition of HSD11β1 suppressed metastatic progression of breast cancer cells. Moreover, 11-hydroxyprogesterone (11-OHP) whom HSD11β1 produced in breast cancer cells, conferred metastatic properties on non-metastatic breast cancer cells through induction of EMT. We identified Peroxisome Proliferator-activated Receptor Alpha (PPAR-α) as essential for both HSD11β1 and 11OHP-driven EMT. Knockdown of PPAR-α induced MET on HSD11β1-expressing breast cancer cells. Taken together, HSD11β1 promotes breast cancer metastasis and would be a novel target for suppressing breast cancer metastasis.

scholarly journals Immune Milieu Established by Postpartum Liver Involution Promotes Breast Cancer Liver Metastasis

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1698
Author(s):  
Alexandra Q. Bartlett ◽  
Nathan D. Pennock ◽  
Alex Klug ◽  
Pepper Schedin
Keyword(s):  
Breast Cancer ◽  
Liver Metastasis ◽  
Tumor Cell ◽  
Cancer Metastasis ◽  
Normal Liver ◽  
Breast Cancer Metastasis ◽  
Matrix Remodeling ◽  
Metastatic Niche ◽  
Mammary Tumor Cells ◽  
Breast Cancer Liver Metastasis

In rodents, we identified a physiologic process within the normal liver that creates a pre-metastatic niche. This physiology is weaning-induced liver involution, characterized by hepatocyte cell death, immune influx, and extracellular matrix remodeling. Here, using weaning-induced liver involution as a model of a physiologically regulated pro-metastatic niche, we investigate how liver involution supports breast cancer metastasis. Liver metastases were induced in BALB/c immune competent hosts by portal vein injection of D2OR (low metastatic) or D2A1 (high metastatic) mouse mammary tumor cells. Tumor incidence and multiplicity increased in involution hosts with no evidence of a proliferation advantage. D2OR tumor cell extravasation, seeding, and early survival were not enhanced in the involuting group compared to the nulliparous group. Rather, the involution metastatic advantage was observed at 14 days post tumor cell injection. This metastatic advantage associated with induction of immune tolerance in the involution host liver, reproductive state dependent intra-tumoral immune composition, and CD8-dependent suppression of metastases in nulliparous hosts. Our findings suggest that the normal postpartum liver is in an immune suppressed state, which can provide a pro-metastatic advantage to circulating breast cancer cells. Potential relevance to women is suggested as a postpartum diagnosis of breast cancer is an independent predictor of liver metastasis.

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