scholarly journals RKIP Suppresses Breast Cancer Metastasis to the Bone by Regulating Stroma-Associated Genes

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Elena Bevilacqua ◽  
Casey A. Frankenberger ◽  
Marsha Rich Rosner
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Interdisciplinary Approach ◽  
Tumor Stroma ◽  
Breast Cancer Metastasis ◽  
Regulatory Mechanisms ◽  
Metastasis Suppressor ◽  
Breast Cancer Patients ◽  
Inhibitory Protein ◽  
Primary Tumors

In the past decade cancer research has recognized the importance of tumorstroma interactions for the progression of primary tumors to an aggressive and invasive phenotype and for colonization of new organs in the context of metastasis. The dialogue between tumor cells and the surrounding stroma is a complex and dynamic phenomenon, as many cell types and soluble factors are involved. While the function of many of the players involved in this cross talk have been studied, the regulatory mechanisms and signaling pathways that control their expression haven’t been investigated in depth. By using a novel, interdisciplinary approach applied to the mechanism of action of the metastasis suppressor, Raf kinase inhibitory protein (RKIP), we identified a signaling pathway that suppresses invasion and metastasis through regulation of stroma-associated genes. Conceptually, the approach we developed uses a master regulator and expression arrays from breast cancer patients to formulate hypotheses based on clinical data. Experimental validation is followed by further bioinformatic analysis to establish the clinical significance of discoveries. Using RKIP as an example we show here that this multi-step approach can be used to identify gene regulatory mechanisms that affect tumor-stroma interactions that in turn influence metastasis to the bone or other organs.

scholarly journals Loss of Breast Cancer Metastasis Suppressor 1 Protein Expression Predicts Reduced Disease-Free Survival in Subsets of Breast Cancer Patients

2006 ◽  
Vol 12 (22) ◽  
pp. 6702-6708 ◽  
Author(s):  
David G. Hicks ◽  
Brian J. Yoder ◽  
Sarah Short ◽  
Shannon Tarr ◽  
Nichole Prescott ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Disease Free Survival ◽  
Breast Cancer Metastasis ◽  
Metastasis Suppressor ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Metastasis Suppressor 1 ◽  
Disease Free ◽  
Breast Cancer Metastasis Suppressor

scholarly journals FOXO3a-driven miRNA signatures suppresses VEGF-A/NRP1 signaling and breast cancer metastasis

Oncogene ◽  
2020 ◽  
Author(s):  
Ying Song ◽  
Shanshan Zeng ◽  
Guopei Zheng ◽  
Danyang Chen ◽  
Pan Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Cancer Metastasis ◽  
Critical Role ◽  
Ectopic Expression ◽  
Breast Cancer Metastasis ◽  
Metastasis Suppressor ◽  
Breast Cancer Patients ◽  
Signaling Axis

AbstractMetastasis remains the major obstacle to improved survival for breast cancer patients. Downregulation of FOXO3a transcription factor in breast cancer is causally associated with the development of metastasis through poorly understood mechanisms. Here, we report that FOXO3a is functionally related to the inhibition of VEGF-A/NRP1 signaling and to the consequent suppression of breast cancer metastasis. We show that FOXO3a directly induces miR-29b-2 and miR-338 expression. Ectopic expression of miR-29b-2/miR-338 significantly suppresses EMT, migration/invasion, and in vivo metastasis of breast cancer. Moreover, we demonstrate that miR-29b-2 directly targets VEGF-A while miR-338 directly targets NRP1, and show that regulation of miR-29b-2 and miR-338 mediates the ability of FOXO3a to suppress VEGF-A/NRP1 signaling and breast cancer metastasis. Clinically, our results show that the FOXO3a-miR-29b-2/miR-338-VEGF-A/NRP1 axis is dysregulated and plays a critical role in disease progression in breast cancer. Collectively, our findings propose that FOXO3a functions as a metastasis suppressor, and define a novel signaling axis of FOXO3a-miRNA-VEGF-A/NRP1 in breast cancer, which might be potential therapeutic targets for breast cancer.

scholarly journals Platinum chemotherapy induces lymphangiogenesis to prime tissues for tumor metastasis

2019 ◽  
Author(s):  
Alexandra R. Harris ◽  
Mohammad S. Azimi ◽  
Robert Cornelison ◽  
Francesca N. Azar ◽  
Danielle C. Llaneza ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cancer Metastasis ◽  
Tumor Stroma ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Treatment Regimens ◽  
Chemotactic Factors ◽  
Breast Cancer Inhibition ◽  
Platinum Chemotherapy

AbstractChemotherapy has been used to inhibit cancer growth for decades, but emerging evidence shows it can affect the tumor stroma unintentionally promoting cancer malignancy. After treatment of primary tumors, remaining drug drains via lymphatics. Though all drugs interact with the lymphatics, we know little of their impact on them. Here, we show a previously unknown effect of platinums, a widely used chemotherapeutic, to directly induce systemic VEGFR3-dependent lymphangiogenesis. These changes are dose-dependent, long-lasting, and occur in healthy and cancerous tissue in multiple mouse models of breast cancer. We saw similar effects in human ovarian and breast cancer patients whose treatment regimens included platinums. Carboplatin treatment results in lymphatic hyperplasia and secretion of pro-chemotactic factors in lymph nodes. Carboplatin treatment of healthy mice prior to mammary tumor inoculation increases cancer metastasis. These findings have broad-reaching implications for cancer patients receiving platinums and support the inclusion of anti-VEGFR3 therapy into treatment regimens.SummaryPlatinum chemotherapy induces lymphangiogenesis priming tissues for metastasis of breast cancer. Inhibition of VEGFR3 via antibody blockade can reverse these effects.

scholarly journals Activation of Nm23-H1 to suppress breast cancer metastasis via redox regulation

2021 ◽  
Author(s):  
Bokyung Kim ◽  
Kong-Joo Lee
Keyword(s):  
Breast Cancer ◽  
Redox Regulation ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Nucleoside Diphosphate Kinase ◽  
Disease Free Survival ◽  
Breast Cancer Metastasis ◽  
Metastasis Suppressor ◽  
Breast Cancer Patients ◽  
Functional Changes

AbstractNon-metastatic protein 23 H1 (Nm23-H1), a housekeeping enzyme, is a nucleoside diphosphate kinase-A (NDPK-A). It was the first identified metastasis suppressor protein. Nm23-H1 prolongs disease-free survival and is associated with a good prognosis in breast cancer patients. However, the molecular mechanisms underlying the role of Nm23-H1 in biological processes are still not well understood. This is a review of recent studies focusing on controlling NDPK activity based on the redox regulation of Nm23-H1, structural, and functional changes associated with the oxidation of cysteine residues, and the relationship between NDPK activity and cancer metastasis. Further understanding of the redox regulation of the NDPK function will likely provide a new perspective for developing new strategies for the activation of NDPK-A in suppressing cancer metastasis.

scholarly journals Reduced RhoA expression enhances breast cancer metastasis with a concomitant increase in CCR5 and CXCR4 chemokines signaling

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Gardiyawasam Kalpana ◽  
Christopher Figy ◽  
Miranda Yeung ◽  
Kam C. Yeung
Keyword(s):  
Breast Cancer ◽  
Primary Tumor ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Tumor Formation ◽  
Receptor Expression ◽  
Mechanistic Study ◽  
Metastasis Suppressor ◽  
Primary Tumors

Abstract The role of RhoA GTPases in breast cancer tumorigenesis and metastasis is unclear. Early studies within which mutations in RhoA were designed based on cancer-associated mutations in Ras supported an oncogene role for RhoA. However, recent whole-genome sequencing studies of cancers raised the possibility that RhoA may have a tumor suppression function. Here, using a syngeneic triple negative breast cancer murine model we investigated the physiological effects of reduced RhoA expression on breast cancer tumorigenesis and metastasis. RhoA knockdown had no effect on primary tumor formation and tumor proliferation, concurring with our in vitro findings where reduced RhoA had no effect on breast cancer cell proliferation and clonogenic growth. In contrast, primary tumors with RhoA knockdown efficiently invaded sentinel lymph nodes and significantly metastasized to lungs compared to control tumors. Mechanistically, the current study demonstrated that this is achieved by promoting a pro-tumor microenvironment, with increased cancer-associated fibroblasts and macrophage infiltration, and by modulating the CCL5-CCR5 and CXCL12-CXCR4 chemokine axes in the primary tumor. To our knowledge, this is the first such mechanistic study in breast cancer showing the ability of RhoA to suppress chemokine receptor expression in breast tumor cells. Our work suggests a physiological lung and lymph node metastasis suppressor role for RhoA GTPase in breast cancer.

scholarly journals Obesity-Activated Lung Stromal Cells Promote Myeloid Lineage Cell Accumulation and Breast Cancer Metastasis

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1005
Author(s):  
Lauren E. Hillers-Ziemer ◽  
Abbey E. Williams ◽  
Amanda Janquart ◽  
Caitlin Grogan ◽  
Victoria Thompson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stromal Cells ◽  
Cancer Metastasis ◽  
Transforming Growth Factor ◽  
Breast Cancer Metastasis ◽  
Tumor Formation ◽  
Obese Mouse ◽  
Obese Mice ◽  
Myeloid Lineage ◽  
Primary Tumors

Obesity is correlated with increased incidence of breast cancer metastasis; however, the mechanisms underlying how obesity promotes metastasis are unclear. In a diet-induced obese mouse model, obesity enhanced lung metastasis in both the presence and absence of primary mammary tumors and increased recruitment of myeloid lineage cells into the lungs. In the absence of tumors, obese mice demonstrated increased numbers of myeloid lineage cells and elevated collagen fibers within the lung stroma, reminiscent of premetastatic niches formed by primary tumors. Lung stromal cells isolated from obese tumor-naïve mice showed increased proliferation, contractility, and expression of extracellular matrix, inflammatory markers and transforming growth factor beta-1 (TGFβ1). Conditioned media from lung stromal cells from obese mice promoted myeloid lineage cell migration in vitro in response to colony-stimulating factor 2 (CSF2) expression and enhanced invasion of tumor cells. Together, these results suggest that prior to tumor formation, obesity alters the lung microenvironment, creating niches conducive to metastatic growth.

A rare solitary breast cancer metastasis to the soft tissue of the ipsilateral arm detected by a physiotherapist: A case report

2021 ◽  
Vol 41 (2) ◽  
pp. 187-191
Author(s):  
Ramesh Omranipour ◽  
Sadaf Alipour ◽  
Bita Eslami
Keyword(s):  
Breast Cancer ◽  
Soft Tissue ◽  
Cancer Metastasis ◽  
Multidisciplinary Treatment ◽  
Breast Cancer Metastasis ◽  
Frequency Interval ◽  
Treatment Team ◽  
Breast Cancer Patients ◽  
Rare Presentation ◽  
Adequate Treatment

BACKGROUND: Late occurrence of solitary soft tissue upper extremity metastasis of breast cancer is very rare. We hereby present a case of metastasis to the biceps muscle of the ipsilateral arm, detected by a physiotherapist six years after mastectomy. The aim of this report is to highlight the rarity of this presentation, to emphasize the role of the physiotherapist as a member of the multidisciplinary treatment team and the possibility of curative treatment despite the poor prognosis. CASE DESCRIPTION: A 2 * 3 cm well-defined isolated metastasis of breast cancer was diagnosed in the left arm of a 31-year-old woman 6 years after successful treatment of her primary tumor. Tumor characteristics, diagnostic plan, and treatment options are discussed. CONCLUSION: Due to its scarcity, there is a lack of knowledge about the frequency, interval, characteristics, best diagnostic modality, adequate treatment, and prognosis of isolated breast cancer metastasis to the soft tissue, and these can be found out by proper reporting. As an important member of the multidisciplinary team in the care and treatment of breast cancer patients, physiotherapists should be aware of this type of rare presentation.

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