scholarly journals Periodontal inflammation recruits distant metastatic breast cancer cells by increasing myeloid-derived suppressor cells

Oncogene ◽  
2019 ◽  
Vol 39 (7) ◽  
pp. 1543-1556 ◽  
Author(s):  
Ran Cheng ◽  
Sandrine Billet ◽  
Chuanxia Liu ◽  
Subhash Haldar ◽  
Diptiman Choudhury ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Periodontal Diseases ◽  
Metastatic Breast ◽  
Metastatic Progression ◽  
Premetastatic Niche ◽  
Periodontal Inflammation

Abstract Periodontal diseases can lead to chronic inflammation affecting the integrity of the tooth supporting tissues. Recently, a striking association has been made between periodontal diseases and primary cancers in the absence of a mechanistic understanding. Here we address the effect of periodontal inflammation (PI) on tumor progression, metastasis, and possible underlining mechanisms. We show that an experimental model of PI in mice can promote lymph node (LN) micrometastasis, as well as head and neck metastasis of 4T1 breast cancer cells, both in early and late stages of cancer progression. The cervical LNs had a greater tumor burden and infiltration of MDSC and M2 macrophages compared with LNs at other sites. Pyroptosis and the resultant IL-1β production were detected in patients with PI, mirrored in mouse models. Anakinra, IL-1 receptor antagonist, limited metastasis, and MDSC recruitment at early stages of tumor progression, but failed to reverse established metastatic tumors. PI and the resulting production of IL-1β was found to promote CCL5, CXCL12, CCL2, and CXCL5 expression. These chemokines recruit MDSC and macrophages, finally enabling the generation of a premetastatic niche in the inflammatory site. These findings support the idea that periodontal inflammation promotes metastasis of breast cancer by recruiting MDSC in part by pyroptosis-induced IL-1β generation and downstream CCL2, CCL5, and CXCL5 signaling in the early steps of metastasis. These studies define the role for IL-1β in the metastatic progression of breast cancer and highlight the need to control PI, a pervasive inflammatory condition in older patients.

scholarly journals Widespread Alternative Splicing Changes in Metastatic Breast Cancer Cells

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 858
Author(s):  
Jagyeong Oh ◽  
Davide Pradella ◽  
Changwei Shao ◽  
Hairi Li ◽  
Namjeong Choi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Alternative Splicing ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Expression Levels

Aberrant alternative splicing (AS) is a hallmark of cancer and a potential target for novel anti-cancer therapeutics. Breast cancer-associated AS events are known to be linked to disease progression, metastasis, and survival of breast cancer patients. To identify altered AS programs occurring in metastatic breast cancer, we perform a global analysis of AS events by using RNA-mediated oligonucleotide annealing, selection, and ligation coupled with next-generation sequencing (RASL-seq). We demonstrate that, relative to low-metastatic, high-metastatic breast cancer cells show different AS choices in genes related to cancer progression. Supporting a global reshape of cancer-related splicing profiles in metastatic breast cancer we found an enrichment of RNA-binding motifs recognized by several splicing regulators, which have aberrant expression levels or activity during breast cancer progression, including SRSF1. Among SRSF1-regulated targets we found DCUN1D5, a gene for which skipping of exon 4 in its pre-mRNA introduces a premature termination codon (PTC), thus generating an unstable transcript degraded by nonsense-mediated mRNA decay (NMD). Significantly, distinct breast cancer subtypes show different DCUN1D5 isoform ratios with metastatic breast cancer expressing the highest level of the NMD-insensitive DCUN1D5 mRNA, thus showing high DCUN1D5 expression levels, which are ultimately associated with poor overall and relapse-free survival in breast cancer patients. Collectively, our results reveal global AS features of metastatic breast tumors, which open new possibilities for the treatment of these aggressive tumor types.

An mRNA processing pathway suppresses metastasis by governing translational control from the nucleus

2021 ◽  
Author(s):  
Albertas Navickas ◽  
Hosseinali Asgharian ◽  
Juliane Winkler ◽  
Lisa Fish ◽  
Kristle Garcia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Translational Control ◽  
Gene Networks ◽  
Breast Cancer Cells ◽  
Metastatic Breast ◽  
Alternative Polyadenylation ◽  
Ribosome Profiling ◽  
Transcriptional Regulatory Mechanisms

Cancer cells often co-opt post-transcriptional regulatory mechanisms to achieve pathologic expression of gene networks that drive metastasis. Translational control is a major regulatory hub in oncogenesis, however its effects on cancer progression remain poorly understood. To address this, we used ribosome profiling to compare genome-wide translation efficiencies of poorly and highly metastatic breast cancer cells and patient-derived xenografts. We developed novel regression-based methods to analyze ribosome profiling and alternative polyadenylation data, and identified HNRNPC as a translational controller of a specific mRNA regulon. Mechanistically, HNRNPC, in concert with PABPC4, binds near to poly(A) signals, thereby governing the alternative polyadenylation of a set of mRNAs. We found that HNRNPC and PABPC4 are downregulated in highly metastatic cells, which causes HNRNPC-bound mRNAs to undergo 3' UTR lengthening and subsequently, translational repression. We showed that modulating HNRNPC expression impacts the metastatic capacity of breast cancer cells in xenograft mouse models. We also found that a small molecule, previously shown to induce a distal-to-proximal poly(A) site switching, counteracts the HNRNPC-PABPC4 driven deregulation of alternative polyadenylation and decreases the metastatic lung colonization by breast cancer cells in vivo.

scholarly journals Role of Estrogen Receptor Signaling in Breast Cancer Metastasis

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Sudipa Saha Roy ◽  
Ratna K. Vadlamudi
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Metastatic Breast ◽  
Estrogen Signaling

Metastatic breast cancer is a life-threatening stage of cancer and is the leading cause of death in advanced breast cancer patients. Estrogen signaling and the estrogen receptor (ER) are implicated in breast cancer progression, and the majority of the human breast cancers start out as estrogen dependent. Accumulating evidence suggests that ER signaling is complex, involving coregulatory proteins and extranuclear actions. ER-coregualtory proteins are tightly regulated under normal conditions with miss expression primarily reported in cancer. Deregulation of ER coregualtors or ER extranuclear signaling has potential to promote metastasis in ER-positive breast cancer cells. This review summarizes the emerging role of ER signaling in promoting metastasis of breast cancer cells, discusses the molecular mechanisms by which ER signaling contributes to metastasis, and explores possible therapeutic targets to block ER-driven metastasis.

scholarly journals Herbal Extract SH003 Suppresses Tumor Growth and Metastasis of MDA-MB-231 Breast Cancer Cells by Inhibiting STAT3-IL-6 Signaling

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Youn Kyung Choi ◽  
Sung-Gook Cho ◽  
Sang-Mi Woo ◽  
Yee Jin Yun ◽  
Sunju Park ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Metastatic Breast ◽  
Herbal Extract ◽  
Tumor Growth And Metastasis ◽  
Risk Of Cancer

Cancer inflammation promotes cancer progression, resulting in a high risk of cancer. Here, we demonstrate that our new herbal extract, SH003, suppresses both tumor growth and metastasis of MDA-MB-231 breast cancer cells via inhibiting STAT3-IL-6 signaling path. Our new herbal formula, SH003, mixed extract fromAstragalus membranaceus, Angelica gigas, andTrichosanthes kirilowiiMaximowicz, suppressed MDA-MB-231 tumor growth and lung metastasisin vivoand reduced the viability and metastatic abilities of MDA-MB-231 cellsin vitro. Furthermore, SH003 inhibited STAT3 activation, which resulted in a reduction of IL-6 production. Therefore, we conclude that SH003 suppresses highly metastatic breast cancer growth and metastasis by inhibiting STAT3-IL-6 signaling path.

scholarly journals Anti-metastatic effect of curcumin analog pentagamaboronon-0-fructose (PGB-0-F) against 4T1 breast cancer cells

2018 ◽  
Vol 23 (2) ◽  
pp. 109
Author(s):  
Yogi Ertanto ◽  
Rohmad Yudi Utomo ◽  
Riris Istighfari Jenie ◽  
Ratna Asmah Susidarti ◽  
Edy Meiyanto
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Chemotherapeutic Agent ◽  
Metastatic Breast ◽  
Gelatin Zymography ◽  
Metastatic Progression ◽  
Curcumin Analog ◽  
Migration Activity ◽  
4T1 Breast Cancer

Development of a chemotherapeutic agent and boron carrying pharmaceutical based on triple-negative breast cancer is important due to its metastatic progression. Metastases are often more dangerous than the primary tumor and they are responsible for 90% of all cancer deaths. The purpose of this study was to explore the anti-metastatic activities of the PGB-0 complex with fructose (PGB-0-F) against 4T1 breast cancer cells. A scratch wound healing assay was carried out to determine the migration inhibition ability of PGB-0-F, while MMP-9 expression was analysed using gelatin zymography. The testing of anti-migration activity showed that PGB-0-F inhibited in 4T1 cells, whereas the gelatin zymography assay revealed a suppression of MMP-9 expression. PGB-0-F inhibited closure on 4T1 metastatic breast cancer cells line compared with the control. PGB-0-F decreased the MMP-9 expression level compared with the control. Based on these results, PGB-0-F has the potential to be developed as a chemotherapeutic agent, and especially as an anti-metastatic agent.

scholarly journals Radiotherapy-Resistant Breast Cancer Cells Enhance Tumor Progression by Enhancing Premetastatic Niche Formation through the HIF-1α-LOX Axis

2020 ◽  
Vol 21 (21) ◽  
pp. 8027
Author(s):  
Young Shin Ko ◽  
Trojan Rugira ◽  
Hana Jin ◽  
Young Nak Joo ◽  
Hye Jung Kim
Keyword(s):  
Breast Cancer ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Environmental Changes ◽  
Lysyl Oxidase ◽  
Hypoxia Inducible Factor ◽  
Therapeutic Resistance ◽  
Premetastatic Niche ◽  
Niche Formation

Cancer stem cells (CSCs) exist in solid tumors and contribute to therapeutic resistance and disease recurrence. Previously, we reported that radiotherapy-resistant (RT-R)-MDA-MB-231 cells from highly metastatic MDA-MB-231 cells produced more CSCs than any other RT-R-breast cancer cells and showed therapeutic resistance and enhanced invasiveness. Hypoxia inducible factor-1α (HIF-1α) induced in the tumor microenvironment leads to the release of lysyl oxidase (LOX), which mediates collagen crosslinking at distant sites to facilitate environmental changes that allow cancer cells to easily metastasize. Therefore, in this study, we investigated whether RT-R-MDA-MB-231 cells induce greater HIF-1α expression, LOX secretion, and premetastatic niche formation than MDA-MB-231 cells do. RT-R-MDA-MB-231 cells increased HIF-1α expression and LOX secretion compared with MDA-MB-231 cells. Mice harboring RT-R-MDA-MB-231 cell xenografts showed enhanced tumor growth and higher expression of the CSC markers, CD44, Notch-4, and Oct3/4. In addition, mice injected with RT-R-MDA-MB-231 cells exhibited a higher level of HIF-1α in tumor tissue, increased secretion of LOX in plasma, higher induced levels of crosslinked collagen, and a higher population of CD11b+ BMDC recruitment around lung tissue, compared with those injected with MDA-MB-231 cells. These results suggest that RT-R-MDA-MB-231 cells contribute to tumor progression by enhancing premetastatic niche formation through the HIF-1α-LOX axis.

scholarly journals OCT4 Suppresses Metastasis in Breast Cancer Cells Through Activation of STAT3 Signaling

2020 ◽  
Author(s):  
Xiangshu Jin ◽  
Yafang Liu ◽  
Huinan Qu ◽  
Da Qi ◽  
Xinqi Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Metastatic Breast ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Oct4 Expression ◽  
Stat3 Signaling

Abstract Background: Metastatic breast cancer is the major cause of death in breast cancer patients. Activation of epithelial-mesenchymal transition (EMT) induces migration and invasion of breast cancer cells (BCCs). OCT4 (POU5F1) is a key transcription factor for reprograming and plays an important role in self-renewal. Recent studies recovered OCT4 may correlate with cancer progression. However, it is no sufficient proofs to verify how OCT4 plays in metastasis of breast cancer. In this present study, we show the role of OCT4 in the migration and invasion of BCCs in vitro and metastasis in vivo.Methods: PCR, Western Blot and Immunofluorescence staining were performed to determine to OCT4 expression in BCCs. Wound-healing assay and invasion assay were utilized to analyze the mobility of BCCs. Tumor metastasis was assessed with nude mice by subcutaneously injection. IHC assay was used to evaluate phosphorylated signal transducer and activator of transcription 3 (p-STAT3) expression in breast cancer tissues and normal breast tissues. To study whether OCT4 regulate EMT through STAT3 signal, we used shRNA to knockdown STAT3 gene expression in BCCs.Results: OCT4 changed cell morphology of BCCs, decreased cell adhesion, and inhibited migration, invasion and metastatic ability of BCCs. In the meantime, overexpression of OCT4 activated STAT3 signaling and changed EMT-related protein expressions in BCCs. However, knockdown of STAT3 in BCCs with overexpression of OCT4 could facilitate EMT.Conclusion: Our data demonstrate that OCT4 suppresses EMT in BCCs through activation of STAT3 signaling, which is a key mechanism in impeding BCCs migration and invasion. Collectively, these data suggest that elevating OCT4 expression may be an effective method for reducing the metastatic potential of BCCs, which could also contribute to developing new methods for diagnosis and new molecular target therapies in breast cancer metastasis.

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.

Sign in / Sign up

Export Citation Format

Share Document