scholarly journals Stromal CCL5 Promotes Breast Cancer Progression by Interacting with CCR3 in Tumor Cells

2021 ◽  
Vol 22 (4) ◽  
pp. 1918
Author(s):  
Mio Yamaguchi ◽  
Kiyoshi Takagi ◽  
Koki Narita ◽  
Yasuhiro Miki ◽  
Yoshiaki Onodera ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Stromal Cells ◽  
Human Breast Carcinoma ◽  
Breast Cancer Patients ◽  
Breast Carcinomas ◽  
Human Breast

Chemokines secreted from stromal cells have important roles for interactions with carcinoma cells and regulating tumor progression. C-C motif chemokine ligand (CCL) 5 is expressed in various types of stromal cells and associated with tumor progression, interacting with C-C chemokine receptor (CCR) 1, 3 and 5 expressed in tumor cells. However, the expression on CCL5 and its receptors have so far not been well-examined in human breast carcinoma tissues. We therefore immunolocalized CCL5, as well as CCR1, 3 and 5, in 111 human breast carcinoma tissues and correlated them with clinicopathological characteristics. Stromal CCL5 immunoreactivity was significantly correlated with the aggressive phenotype of breast carcinomas. Importantly, this tendency was observed especially in the CCR3-positive group. Furthermore, the risk of recurrence was significantly higher in the patients with breast carcinomas positive for CCL5 and CCR3 but negative for CCR1 and CCR5, as compared with other patients. In summary, the CCL5-CCR3 axis might contribute to a worse prognosis in breast cancer patients, and these findings will contribute to a better understanding of the significance of the CCL5/CCRs axis in breast carcinoma microenvironment.

scholarly journals Sex steroid-producing enzymes in human breast cancer

2005 ◽  
Vol 12 (4) ◽  
pp. 701-720 ◽  
Author(s):  
Takashi Suzuki ◽  
Yasuhiro Miki ◽  
Yasuhiro Nakamura ◽  
Takuya Moriya ◽  
Kiyoshi Ito ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Cancer Patients ◽  
Stromal Cells ◽  
Cellular Localization ◽  
Sex Steroid ◽  
Breast Cancer Patients ◽  
Human Breast ◽  
Estrogen Production ◽  
Aromatase Mrna

It is well known that sex steroids are involved in the growth of breast cancers, and the great majority of breast carcinomas express estrogen (ER), progesterone (PR), and androgen (AR) receptors. In particular, recent studies have demonstrated that estrogens and androgens are locally produced in breast carcinoma tissues, and total blockade of in situ estrogen production potentially leads to an improvement in prognosis of breast cancer patients. Therefore, it is important to obtain a better understanding of sex steroid-producing enzymes in breast carcinoma tissues. In this review, we summarize recent studies on the expression and regulation of enzymes related to intratumoral production of estrogens (aromatase, 17β-hydroxysteroid dehydrogenase type 1 (17βHSD1), and steroid sulfatase (STS) etc) and androgens (17βHSD5 and 5α-reductase) in human breast carcinoma tissues, and discuss the biological and/or clinical significance of these enzymes. The cellular localization of aromatase in breast carcinoma tissues still remains controversial. Therefore, we examined localization of aromatase mRNA in breast carcinoma tissues by laser capture microdissection/real time-polymerase chain reaction. Aromatase mRNA expression was detected in both carcinoma and intratumoral stromal cells, and the expression level of aromatase mRNA was higher in intratumoral stromal cells than in carcinoma cells in the cases examined. We also examined an association among the immunoreactivity of enzymes related to intratumoral estrogen production and ERs in breast carcinoma tissues, but no significant association was detected. Therefore, the enzymes responsible for the intratumoral production of estrogen may not always be the same among breast cancer patients, and not only aromatase but also other enzymes such as STS and 17βHSD1 may have important therapeutic potential as targets for endocrine therapy in breast cancer patients.

scholarly journals Krüppel-like factor 5 in human breast carcinoma: a potent prognostic factor induced by androgens

2012 ◽  
Vol 19 (6) ◽  
pp. 741-750 ◽  
Author(s):  
Kiyoshi Takagi ◽  
Yasuhiro Miki ◽  
Yoshiaki Onodera ◽  
Yasuhiro Nakamura ◽  
Takanori Ishida ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factor ◽  
Breast Carcinoma ◽  
Carcinoma Cells ◽  
Human Breast Carcinoma ◽  
Dependent Manner ◽  
Breast Carcinomas ◽  
Human Breast ◽  
Breast Carcinoma Cells ◽  
Mcf 7

Krüppel-like factor 5 (intestinal) or Krüppel-like factor 5 (KLF5) is a zinc finger-containing transcription factor and involved in important biological processes including cell proliferation and differentiation. However, clinical significance of KLF5 protein has remained largely unknown in breast cancer. Therefore, in this study, we immunolocalized KLF5 in 113 human breast carcinoma cases. KLF5 immunoreactivity was frequently detected in the nuclei of breast carcinoma cells, and median value of the ratio of KLF5-positive carcinoma cells was 30% and was positively associated with the status of androgen receptor. KLF5 immunoreactivity was also significantly associated with increased risk of recurrence and worse clinical outcome in breast cancer patients by univariate analyses, and subsequent multivariate analyses demonstrated that KLF5 immunoreactivity was an independent prognostic factor for both disease-free and breast cancer-specific survival of the patients. We then examined possible regulation of KLF5 by androgen using MCF-7 breast carcinoma cells. KLF5 mRNA was induced by biologically active androgen 5α-dihydrotestosterone in a dose- and time-dependent manner in MCF-7 cells. In addition, results of transfection experiments demonstrated that proliferation activity of MCF-7 cells was significantly associated with the KLF5 expression level. These findings suggest that KLF5 is an androgen-responsive gene in human breast carcinomas and play important roles in the progression of breast carcinomas. KLF5 immunoreactivity is therefore considered a potent prognostic factor in human breast cancers.

scholarly journals Iron-Bound Lipocalin-2 from Tumor-Associated Macrophages Drives Breast Cancer Progression Independent of Ferroportin

Metabolites ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 180
Author(s):  
Christina Mertens ◽  
Matthias Schnetz ◽  
Claudia Rehwald ◽  
Stephan Grein ◽  
Eiman Elwakeel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Lung Metastases ◽  
Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Lipocalin 2 ◽  
Tumor Associated Macrophages

Macrophages supply iron to the breast tumor microenvironment by enforced secretion of lipocalin-2 (Lcn-2)-bound iron as well as the increased expression of the iron exporter ferroportin (FPN). We aimed at identifying the contribution of each pathway in supplying iron for the growing tumor, thereby fostering tumor progression. Analyzing the expression profiles of Lcn-2 and FPN using the spontaneous polyoma-middle-T oncogene (PyMT) breast cancer model as well as mining publicly available TCGA (The Cancer Genome Atlas) and GEO Series(GSE) datasets from the Gene Expression Omnibus database (GEO), we found no association between tumor parameters and Lcn-2 or FPN. However, stromal/macrophage-expression of Lcn-2 correlated with tumor onset, lung metastases, and recurrence, whereas FPN did not. While the total iron amount in wildtype and Lcn-2−/− PyMT tumors showed no difference, we observed that tumor-associated macrophages from Lcn-2−/− compared to wildtype tumors stored more iron. In contrast, Lcn-2−/− tumor cells accumulated less iron than their wildtype counterparts, translating into a low migratory and proliferative capacity of Lcn-2−/− tumor cells in a 3D tumor spheroid model in vitro. Our data suggest a pivotal role of Lcn-2 in tumor iron-management, affecting tumor growth. This study underscores the role of iron for tumor progression and the need for a better understanding of iron-targeted therapy approaches.

Multifunctional Nanoparticles Loaded with Vascular Endothelial Growth Factor Inhibitors and MED1 siRNA to Inhibit Breast Cancer Progression by Targeting Tumor-Associated Macrophages and Breast Cancer Cells

2021 ◽  
Vol 17 (12) ◽  
pp. 2364-2373
Author(s):  
Song Wang ◽  
Zifeng Luo ◽  
Xinke Zhou ◽  
Chong Wang ◽  
Yuanwei Luo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Fluorescence Analysis ◽  
Cell Uptake ◽  
Breast Cancer Patients ◽  
Drug Encapsulation ◽  
Vegf Inhibitors ◽  
Proliferation And Invasion

Breast cancer is still threatening many people’ lives, hence novel targeted therapies are urgently required to improve the poor outcome of breast cancer patients. Herein, our study aimed to explore the potential of nanoparticles (NPs)-loaded with VEGF inhibitors and MED1 siRNA for treatment of the disorder. PEG and MTC conjugates were synthesized by ion gelation, and equipped with VEGF inhibitor (siV) and MED1 (siD) siRNA (MT/PC/siV-D NPs). The size and morphology of the NPs were detected by TEM. Agarose gel experiment was performed to detect drug encapsulation rate and NPs stability. Zeta potential was assessed by immunofluorescence assay and cell uptake was detected by fluorescence analysis. After cancer cells were treated with NPs or PBS, cell proliferation and invasion were evaluated with VEGF and MED1 expression was detected by Western blot and RT-qPCR analyses. Animal model was conducted to confirm the role of NPs in tumor growth. Results showed that, the MT/PC/siV-D NPs exhibited great stability, drug encapsulation and internalization ability. The combined NPs caused decreased proliferation and invasion of tumor cells, inducing M2 macrophages to re-polarize to M1 type with declined expression of VEGF and MED1. Moreover, the NPs remarkably alleviated breast tumor progression. The multifunctional NPs equipped with EGF inhibitors and MED1 siRNA can inhibit tumor progression by targeting TAMs and cancer cells during breast cancer.

Expression of the C-Met/HGF receptor in human breast carcinoma: Correlation with tumor progression

1997 ◽  
Vol 74 (3) ◽  
pp. 301-309 ◽  
Author(s):  
Lucia Beviglia ◽  
Kentaro Matsumoto ◽  
Ching-Shwun Lin ◽  
Barry L. Ziober ◽  
Randall H. Kramer
Keyword(s):  
Breast Carcinoma ◽  
Tumor Progression ◽  
Human Breast Carcinoma ◽  
Human Breast

scholarly journals Potential Involvement of Jagged1 in Metastatic Progression of Human Breast Carcinomas

2016 ◽  
Vol 62 (2) ◽  
pp. 378-386 ◽  
Author(s):  
Natalia Bednarz-Knoll ◽  
Antonia Efstathiou ◽  
Frauke Gotzhein ◽  
Harriet Wikman ◽  
Volkmar Mueller ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Cancer Patients ◽  
Progressive Disease ◽  
Metastatic Progression ◽  
Breast Cancer Patients ◽  
Breast Carcinomas ◽  
Human Breast ◽  
Free Survival ◽  
Human Breast Carcinomas

Abstract BACKGROUND Jagged1, the ligand of Notch, has been shown to be involved in formation of bone metastases in an experimental study. Here, clinical relevance of Jagged1 expression in tumor progression was assessed in human breast carcinomas. METHODS Jagged1 expression was evaluated by immunohistochemistry in 228 tumor tissue samples and compared to clinicopathologic parameters and patients' outcomes. Furthermore, circulating tumor cells (CTCs) from peripheral blood of 100 unmatched metastatic cancer patients with progressive disease were enriched using Ficoll density gradient centrifugation and detected by pan-keratin/Jagged1/CD45 immunofluorescent staining. RESULTS Jagged1 expression was detected in 50% of 228 tumors. Jagged1 expression was correlated with higher tumor grade (P = 0.047), vascular invasion (P = 0.026), luminal B subtype (P = 0.016), overexpression of Her-2 (P = 0.001), high Ki-67 expression (P = 0.035), and aldehyde dehydrogenase 1 (ALDH1) positivity (P = 0.013). Jagged 1 expression indicated shorter disease-free survival (DFS) (P = 0.040) and metastasis-free survival (P = 0.048) in lymph node–negative breast cancer for which it was the only independent predictor of DFS (multivariate analysis, P = 0.046). Tumors characterized by the strongest Jagged1 staining intensity (7.5% of cases) correlated with lymph node positivity (P = 0.037), metastatic relapse (P = 0.049), and higher number of disseminated tumor cells in bone marrow aspirates (P = 0.041). Twenty-one unmatched metastatic breast cancer patients with progressive disease were positive for CTCs, and 85.7% of the CTCs also expressed Jagged1. The presence of Jagged1(+) CTCs was significantly associated with shorter progression-free survival in patients treated with bisphosphonates (P = 0.013). CONCLUSIONS Jagged1 expression characterizes more aggressive breast carcinoma and might be involved in tumor cell dissemination, metastatic progression, and resistance to bone-targeting therapy in breast cancer patients.

Molecular profiling of circulating tumor cells in the peripheral blood of patients with primary and metastatic breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 20033-20033
Author(s):  
N. Fersis ◽  
V. Deckwart ◽  
A. Leitz ◽  
M. Weber ◽  
J. Rom ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Breast Carcinoma ◽  
Tumor Cell ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Rt Pcr ◽  
Her 2

20033 Background: The purpose of this study was detection and expression profiling of circulating tumor cells (CTC) in breast cancer patients. Methods: Two separate probes of 5 mL peripheral EDTA-blood from patients with primary breast cancer (n=167) and metastatic disease (n=111) were used for immunomagnetic tumor cell selection. Targets for preanalytical enrichment were the antigens EpCAM and MUC-1. Separated cells were lysed and used for mRNA isolation and c-DNA synthesis. The breast carcinoma-associated transcripts EpCAM, MUC-1, HER-2, claudin7, cytokeratin 19, mammaglobin 1, prostate-specific ets factor (PSE) and survivin were amplified by three separate multiplex RT-PCR reactions. Amplicons were analysed by capillary electrophoresis with the Agilent Bioanalyzer 2100. Specificity of the RT-PCR was confirmed by examination of blood of healthy donors. Results: Sensitivity for every single transcript was adjusted to 2 tumor cells per 5 ml blood. Tumor-associated transcripts were detected in 31 of of 167 (18.5%) patients with primary breast cancer and in 46 of 111 (41%) patients with metastatic disease. The marker with the highest incidence in both groups was MUC-1, with a positivity rate of 81%. Tumor-associated transcripts were heterogenouosly expressed, however multiple markers were identified in more than 50% of the positive samples. Conclusion: Using a combination of preanalytical immunomagnetic tumor cell enrichment followed by a multigen RT-PCR approach we describe a sensitive detection system for breast carcinoma cells. In this study a panel of 8 genes overexpressed at high levels in metastatic breast cancer was selected for the identification of disseminated tumor cells in the peripheral blood of breast cancer patients. HER-2, survivin as a unique member of the inhibitor of apotosis protein family, as well as PSE identified in circulating breast cancer cells may serve as prognostic indicators of tumor progression and could represent valid targets for new individualized therapeutic interventions. No significant financial relationships to disclose.

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