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Yibin Kang - One of the best experts on this subject based on the ideXlab platform.

  • the biology of Bone Metastasis
    Cold Spring Harbor Perspectives in Medicine, 2018
    Co-Authors: Mark Esposito, Theresa A Guise, Yibin Kang
    Abstract:

    Bone Metastasis, or the development of secondary tumors within the Bone of cancer patients, is a debilitating and incurable disease. Despite its morbidity, the biology of Bone Metastasis represents one of the most complex and intriguing of all oncogenic processes. This complexity derives from the intricately organized Bone microenvironment in which the various stages of hematopoiesis, osteogenesis, and osteolysis are jointly regulated but spatially restricted. Disseminated tumor cells (DTCs) from various common malignancies such as breast, prostate, lung, and kidney cancers or myeloma are uniquely primed to subvert these endogenous Bone stromal elements to grow into pathological osteolytic or osteoblastic lesions. This colonization process can be separated into three key steps: seeding, dormancy, and outgrowth. Targeting the processes of dormancy and initial outgrowth offers the most therapeutic promise. Here, we discuss the concepts of the Bone Metastasis niche, from controlling tumor-cell survival to growth into clinically detectable disease.

  • targeting tumor stromal interactions in Bone Metastasis
    Pharmacology & Therapeutics, 2014
    Co-Authors: Mark Esposito, Yibin Kang
    Abstract:

    Bone Metastasis is a frequent occurrence in late stage solid tumors, including breast cancers, prostate or lung. However, the causes for this proclivity have only recently been elucidated. Significant progress has been made in the past decade toward understanding the molecular underpinnings of Bone Metastasis, and much of this research reveals a crucial role of the host stroma in each step of the metastatic cascade. Tumor-stromal interactions are crucial in engineering a pre-metastatic niche, accommodating metastatic seeding, and establishing the vicious cycle of Bone Metastasis. Current treatments in Bone Metastasis focus on latter steps of the metastatic cascade, with most treatments targeting the process of Bone remodeling; however, emerging research identifies many other candidates as promising targets. Host stromal cells including platelets and endothelial cells are important in the early steps of metastatic homing, attachment and extravasation while a variety of immune cells, parenchymal cells and mesenchymal cells of the Bone marrow are important in the establishment of overt, immune-suppressed metastatic lesions. Many participants during these steps have been identified and functionally validated. Significant contributors include integrins, (αvβ3, α2β1, α4β1), TGFβ family members, Bone resident proteins (BSP, OPG, SPARC, OPN), RANKL, and PTHrP. In this review, we will discuss the contribution of host stromal cells to pre-metastatic niche conditioning, seeding, dormancy, Bone-remodeling, immune regulation, and chemotherapeutic shielding in Bone Metastasis. Research exploring these interactions between Bone metastases and stromal cells has yielded many therapeutic targets, and we will discuss both the current and future therapeutic avenues in treating Bone Metastasis.

  • Global secretome analysis identifies novel mediators of Bone Metastasis
    Cell Research, 2012
    Co-Authors: Mario Andres Blanco, Gary Leroy, Zia Khan, Maša Alečković, Barry M Zee, Benjamin A Garcia, Yibin Kang
    Abstract:

    Bone is the one of the most common sites of distant Metastasis of solid tumors. Secreted proteins are known to influence pathological interactions between metastatic cancer cells and the Bone stroma. To comprehensively profile secreted proteins associated with Bone Metastasis, we used quantitative and non-quantitative mass spectrometry to globally analyze the secretomes of nine cell lines of varying Bone metastatic ability from multiple species and cancer types. By comparing the secretomes of parental cells and their Bone metastatic derivatives, we identified the secreted proteins that were uniquely associated with Bone Metastasis in these cell lines. We then incorporated bioinformatic analyses of large clinical Metastasis datasets to obtain a list of candidate novel Bone Metastasis proteins of several functional classes that were strongly associated with both clinical and experimental Bone Metastasis. Functional validation of selected proteins indicated that in vivo Bone Metastasis can be promoted by high expression of (1) the salivary cystatins CST1, CST2, and CST4; (2) the plasminogen activators PLAT and PLAU; or (3) the collagen functionality proteins PLOD2 and COL6A1. Overall, our study has uncovered several new secreted mediators of Bone Metastasis and therefore demonstrated that secretome analysis is a powerful method for identification of novel biomarkers and candidate therapeutic targets.

  • tumor derived jagged1 promotes osteolytic Bone Metastasis of breast cancer by engaging notch signaling in Bone cells
    Cancer Cell, 2011
    Co-Authors: Nilay Sethi, Xudong Dai, Christopher Winter, Yibin Kang
    Abstract:

    Despite evidence supporting an oncogenic role in breast cancer, the Notch pathway's contribution to Metastasis remains unknown. Here, we report that the Notch ligand Jagged1 is a clinically and functionally important mediator of Bone Metastasis by activating the Notch pathway in Bone cells. Jagged1 promotes tumor growth by stimulating IL-6 release from osteoblasts and directly activates osteoclast differentiation. Furthermore, Jagged1 is a potent downstream mediator of the Bone Metastasis cytokine TGFβ that is released during Bone destruction. Importantly, γ-secretase inhibitor treatment reduces Jagged1-mediated Bone Metastasis by disrupting the Notch pathway in stromal Bone cells. These findings elucidate a stroma-dependent mechanism for Notch signaling in breast cancer and provide rationale for using γ-secretase inhibitors for the treatment of Bone Metastasis.

  • adamts1 and mmp1 proteolytically engage egf like ligands in an osteolytic signaling cascade for Bone Metastasis
    Genes & Development, 2009
    Co-Authors: Qiongqing Wang, Yibin Kang, Catherine Van Poznak, Martin Fleisher, Michael Reiss, Joan Massague
    Abstract:

    Bone Metastasis is mediated by complex interactions between tumor cells and resident stromal cells in the Bone microenvironment. The functions of metalloproteinases in organ-specific Metastasis remain poorly defined despite their well-appreciated role in matrix degradation and tumor invasion. Here, we show a mechanism whereby two distinct metalloproteinases, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS1) and matrix metalloproteinase-1 (MMP1), orchestrate a paracrine signaling cascade to modulate the Bone microenvironment in favor of osteoclastogenesis and Bone Metastasis. Proteolytic release of membrane-bound epidermal growth factor (EGF)-like growth factors, including Amphiregulin (AREG), heparin-binding EGF (HB-EGF), and transforming growth factor α (TGFα) from tumor cells suppress the expression of osteoprotegerin (OPG) in osteoblasts and subsequently potentiate osteoclast differentiation. EGF receptor (EGFR) inhibitors block osteolytic Bone Metastasis by targeting EGFR signaling in Bone stromal cells. Furthermore, elevated MMP1 and ADAMTS1 expression is associated with increased risk of Bone Metastasis in breast cancer patients. This study established MMP1 and ADAMTS1 in tumor cells, as well as EGFR signaling in osteoblasts, as promising therapeutic targets for inhibiting Bone Metastasis of breast cancer.

Joan Massague - One of the best experts on this subject based on the ideXlab platform.

  • adamts1 and mmp1 proteolytically engage egf like ligands in an osteolytic signaling cascade for Bone Metastasis
    Genes & Development, 2009
    Co-Authors: Qiongqing Wang, Yibin Kang, Catherine Van Poznak, Martin Fleisher, Michael Reiss, Joan Massague
    Abstract:

    Bone Metastasis is mediated by complex interactions between tumor cells and resident stromal cells in the Bone microenvironment. The functions of metalloproteinases in organ-specific Metastasis remain poorly defined despite their well-appreciated role in matrix degradation and tumor invasion. Here, we show a mechanism whereby two distinct metalloproteinases, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS1) and matrix metalloproteinase-1 (MMP1), orchestrate a paracrine signaling cascade to modulate the Bone microenvironment in favor of osteoclastogenesis and Bone Metastasis. Proteolytic release of membrane-bound epidermal growth factor (EGF)-like growth factors, including Amphiregulin (AREG), heparin-binding EGF (HB-EGF), and transforming growth factor α (TGFα) from tumor cells suppress the expression of osteoprotegerin (OPG) in osteoblasts and subsequently potentiate osteoclast differentiation. EGF receptor (EGFR) inhibitors block osteolytic Bone Metastasis by targeting EGFR signaling in Bone stromal cells. Furthermore, elevated MMP1 and ADAMTS1 expression is associated with increased risk of Bone Metastasis in breast cancer patients. This study established MMP1 and ADAMTS1 in tumor cells, as well as EGFR signaling in osteoblasts, as promising therapeutic targets for inhibiting Bone Metastasis of breast cancer.

  • latent Bone Metastasis in breast cancer tied to src dependent survival signals
    Cancer Cell, 2009
    Co-Authors: Xiang Zhang, Qiongqing Wang, Joan Massague, William L Gerald, Clifford A Hudis, Larry Norton, Marcel Smid, John A Foekens
    Abstract:

    Metastasis may arise years after removal of a primary tumor. The mechanisms allowing latent disseminated cancer cells to survive are unknown. We report that a gene expression signature of Src activation is associated with late-onset Bone Metastasis in breast cancer. This link is independent of hormone receptor status or breast cancer subtype. In breast cancer cells, Src is dispensable for homing to the Bones or lungs but is critical for the survival and outgrowth of these cells in the Bone marrow. Src mediates AKT regulation and cancer cell survival responses to CXCL12 and TNF-related apoptosis-inducing ligand (TRAIL), factors that are distinctively expressed in the Bone Metastasis microenvironment. Breast cancer cells that lodge in the Bone marrow succumb in this environment when deprived of Src activity.

  • abstract 5667 adamts1 and mmp1 promote breast cancer Bone Metastasis through a Bone stromal cell mediated osteolytic signaling cascade
    Cancer Research, 2009
    Co-Authors: Qiongqing Wang, Catherine Van Poznak, Martin Fleisher, Michael Reiss, Joan Massague, Yibin Kang
    Abstract:

    AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO Bone Metastasis is mediated by complex interactions between tumor cells and resident stromal cells in the Bone microenvironment. The functions of metalloproteinases in Bone-specific Metastasis remain poorly defined despite their well-appreciated role in matrix degradation, tumor invasion and tumor-stroma interaction. Here, we show that two distinct metalloproteinases, ADAMTS1 and MMP1, synergistically promote breast cancer Bone Metastasis by modulating the Bone microenvironment to favor osteoclastogenesis. ADAMTS1 and MMP1 proteolytically release EGF-like growth factors, including Amphiregulin, HB-EGF and TGFa, from tumor cells. The released EGF-like growth factors suppress the expression of Osteoprotegerin in osteoblasts and subsequently potentiate osteoclast differentiation. Activated osteoclasts process the Bone matrix and release various growth factors which further support the proliferation of the tumor cells in the Bone. Simultaneous gene silencing of ADAMTS1 and MMP1 by short-hairpin RNA in highly Bone-metastatic variants of the human breast cancer cell MDA-MB-231 inhibits the progression of osteolytic Bone Metastasis in the mouse model, whereas co-overexpression of ADAMTS1 and MMP1 in the lowly metastatic variants of MDA-MB-231 promotes Bone Metastasis. Targeting EGFR signaling in Bone stromal cells with EGFR inhibitors also blocks osteolytic Bone Metastasis by the strong Bone-metastatic variants of MDA-MB-231, even though the orthotopic tumor growth is unaffected. Besides in MDA-MB-231, ADAMTS1 and MMP1 were found to be overexpressed in the in vivo selected variants of primary breast tumor cells which preferentially colonize the Bone. Elevated MMP1 and ADAMTS1 expression was significantly associated with increased risk of Bone Metastasis in breast cancer patients. Our study presents, for the first time, a mechanism whereby two distinct metalloproteinases orchestrate a paracrine signaling cascade to promote Bone Metastasis. This study established ADAMTS1 and MMP1, as well as EGFR signaling in osteoblasts, as promising therapeutic targets for inhibiting Bone Metastasis of breast cancer. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5667.

  • breast cancer Bone Metastasis mediated by the smad tumor suppressor pathway
    Proceedings of the National Academy of Sciences of the United States of America, 2005
    Co-Authors: Yibin Kang, William L Gerald, Shaun Tulley, Gaorav P Gupta, Inna Serganova, Chang Rung Chen, Katia Manovatodorova, Ronald G Blasberg, Joan Massague
    Abstract:

    TGF-β can signal by means of Smad transcription factors, which are quintessential tumor suppressors that inhibit cell proliferation, and by means of Smad-independent mechanisms, which have been implicated in tumor progression. Although Smad mutations disable this tumor-suppressive pathway in certain cancers, breast cancer cells frequently evade the cytostatic action of TGF-β while retaining Smad function. Through immunohistochemical analysis of human breast cancer Bone metastases and functional imaging of the Smad pathway in a mouse xenograft model, we provide evidence for active Smad signaling in human and mouse Bone-metastatic lesions. Genetic depletion experiments further demonstrate that Smad4 contributes to the formation of osteolytic Bone metastases and is essential for the induction of IL-11, a gene implicated in Bone Metastasis in this mouse model system. Activator protein-1 is a key participant in Smad-dependent transcriptional activation of IL-11 and its overexpression in Bone-metastatic cells. Our findings provide functional evidence for a switch of the Smad pathway, from tumor-suppressor to prometastatic, in the development of breast cancer Bone Metastasis.

Jianru Xiao - One of the best experts on this subject based on the ideXlab platform.

  • microrna 124 inhibits Bone Metastasis of breast cancer by repressing interleukin 11
    Molecular Cancer, 2018
    Co-Authors: Weiluo Cai, Wending Huang, Tianrui Chen, Chenglong Zhao, Wangjun Yan, Jianru Xiao
    Abstract:

    Most patients with breast cancer in advanced stages of the disease suffer from Bone metastases which lead to fractures and nerve compression syndromes. microRNA dysregulation is an important event in the metastases of breast cancer to Bone. microRNA-124 (miR-124) has been proved to inhibit cancer progression, whereas its effect on Bone metastases of breast cancer has not been reported. Therefore, this study aimed to investigate the role and underlying mechanism of miR-124 in Bone metastases of breast cancer. In situ hybridization (ISH) was used to detect the expression of miR-124 in breast cancer tissues and Bone metastatic tissues. Ventricle injection model was constructed to explore the effect of miR-124 on Bone Metastasis in vivo. The function of cancer cell derived miR-124 in the differentiation of osteoclast progenitor cells was verified in vitro. Dual-luciferase reporter assay was conducted to confirm Interleukin-11 (IL-11) as a miR-124 target. The involvement of miR-124/IL-11 in the prognosis of breast cancer patients with Bone Metastasis was determined by Kaplan-Meier analysis. Herein, we found that miR-124 was significantly reduced in metastatic Bone tissues from breast cancers. Down-regulation of miR-124 was associated with aggressive clinical characteristics and shorter Bone Metastasis-free survival and overall survival. Restoration of miR-124 suppressed, while inhibition of miR-124 promoted the Bone Metastasis of breast cancer cells in vivo. At the cellular level, gain of function and loss-of function assays indicated that cancer cell-derived miR-124 inhibited the survival and differentiation of osteoclast progenitor cells. At the molecular level, we demonstrated that IL-11 partially mediated osteoclastogenesis suppression by miR-124 using in vitro and in vivo assays. Furthermore, IL-11 levels were inversely correlated with miR-124, and up-regulation IL-11 in Bone metastases was associated with a poor prognosis. Thus, the identification of a dysregulated miR-124/IL-11 axis helps elucidate mechanisms of breast cancer metastases to Bone, uncovers new prognostic markers, and facilitates the development of novel therapeutic targets to treat and even prevent Bone metastases of breast cancer.

  • xcr1 promotes cell growth and migration and is correlated with Bone Metastasis in non small cell lung cancer
    Biochemical and Biophysical Research Communications, 2015
    Co-Authors: Ting Wang, Wangjun Yan, Shuai Han, Zhitao Han, Tielong Liu, Haifeng Wei, Dianwen Song, Wang Zhou, Xinghai Yang, Jianru Xiao
    Abstract:

    Bone Metastasis occurs in approximately 30-40% patients with advanced non-small cell lung cancer (NSCLC), but the mechanism underlying this Bone Metastasis remains poorly understood. The chemokine super family is believed to play an important role in tumor Metastasis in lung cancer. The chemokine receptor XCR1 has been identified to promote cell proliferation and migration in oral cancer and ovarian carcinoma, but the role of XCR1 in lung cancer has not been reported. In this study, we demonstrated for the first time that XCR1 was overexpressed in lung cancer Bone Metastasis as compared with that in patients with primary lung cancer. In addition, the XCR1 ligand XCL1 promoted the proliferation and migration of lung cancer cells markedly, and knockdown of XCR1 by siRNA abolished the effect of XCL1 in cell proliferation and migration. Furthermore, we identified JAK2/STAT3 as a novel downstream pathway of XCR1, while XCL1/XCR1 increased the mRNA level of the downstream of JAK2/STAT3 including PIM1, JunB, TTP, MMP2 and MMP9. These results indicate that XCR1 is a new potential therapeutic target for the treatment of lung cancer Bone Metastasis.

  • trifolium like platinum nanoparticle mediated photothermal therapy inhibits tumor growth and osteolysis in a Bone Metastasis model
    Small, 2015
    Co-Authors: Changping Wang, Wangjun Yan, Jianru Xiao, Xiaopan Cai, Jishen Zhang, Xinyu Wang, Yu Wang, Quan Huang, Qiang Zhang, Yiyun Cheng
    Abstract:

    Bone Metastasis is a frequent and fatal complication of cancer that lacks effective clinical treatment. Photothermal therapy represents a new strategy for the destruction of multiple cancers. In this study, trifolium-like platinum nanoparticles (TPNs) with small size and excellent photothermal conversion property are prepared via a facile and green method. TPNs show minimal cytotoxicity on normal cell lines and kill cancer cells upon exposure to a near-infrared light. These nanoparticles effectively inhibit tumor growth and prevent osteolysis in a Bone Metastasis model. This study offers a promising strategy in the treatment of Bone Metastasis.

Meredith L Kilgore - One of the best experts on this subject based on the ideXlab platform.

  • mortality following Bone Metastasis and skeletal related events among women with breast cancer a population based analysis of u s medicare beneficiaries 1999 2006
    Breast Cancer Research and Treatment, 2012
    Co-Authors: Nalini Sathiakumar, Elizabeth Delzell, Michael A Morrisey, Carla I Falkson, Mellissa Yong, Victoria M Chia, Justin Blackburn, Tarun Arora, Ilene Brill, Meredith L Kilgore
    Abstract:

    The aim of the study is to quantify the impact of Bone Metastasis and skeletal-related events (SREs) on mortality in older breast cancer patients. Using the linked Surveillance, Epidemiology and End Results-Medicare database, we identified women aged 65 years or older diagnosed with breast cancer between July 1, 1999 and December 31, 2005 and followed them to determine deaths occurring through December 31, 2006. We classified patients as having possible Bone Metastasis and SREs using discharge diagnoses from inpatient claims and diagnoses paired with procedure codes from outpatient claims. We used Cox regression to estimate mortality hazards ratios (HR) among women with Bone Metastasis with or without SRE, compared with women without Bone Metastasis. Among 98,260 women with breast cancer (median follow-up, 3.3 years), 7,189 (7.3%) had Bone Metastasis either at breast cancer diagnosis (1.5%) or during follow-up (5.8%). SREs occurred in 3,319 (46%) of women with Bone Metastasis. HRs for risk of death were 4.9 (95% CI 4.7-5.1) and 6.2 (95% CI 5.9-6.5), respectively, for women with Bone Metastasis but no SRE and for women with Bone Metastasis plus SRE, compared with women without Bone Metastasis. In analyses restricted to women with Bone Metastasis, the adjusted HR was 1.5 (95% CI 1.4-1.6) for women with Bone Metastasis plus SRE, compared with women with Bone Metastasis but without SRE. Having a Bone Metastasis, as indicated by Medicare claims, was associated strongly with mortality among women with breast cancer. This association was stronger for Bone Metastasis complicated by SRE than for Bone Metastasis without SRE.

  • mortality following Bone Metastasis and skeletal related events among men with prostate cancer a population based analysis of us medicare beneficiaries 1999 2006
    Prostate Cancer and Prostatic Diseases, 2011
    Co-Authors: Nalini Sathiakumar, Elizabeth Delzell, Michael A Morrisey, Carla I Falkson, Mellissa Yong, Victoria M Chia, Justin Blackburn, Tarun Arora, Meredith L Kilgore
    Abstract:

    Information on the impact of Bone Metastasis and skeletal-related events (SREs) on mortality among prostate cancer patients is limited. Using the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database, we identified men aged 65 years or older diagnosed with prostate cancer between July 1 1999 and December 31 2005 and followed to determine deaths through December 31 2006. We classified subjects as having Bone Metastasis and SREs as indicated by Medicare claims. Using Cox regression, we estimated mortality hazards ratios (HR) among men with Bone Metastasis with or without SRE, compared with men without Bone Metastasis. Among 126,978 men with prostate cancer (median follow-up, 3.3 years), 9746 (7.7%) had Bone Metastasis at prostate cancer diagnosis (1.7%) or during follow-up (5.9%). SREs occurred in 4296 (44%) men with Bone Metastasis. HRs for risk of death were 6.6 (95% CI=6.4-6.9) and 10.2 (95% CI=9.8-10.7), respectively, for men with Bone Metastasis but no SRE and for men with Bone Metastasis plus SRE, compared with men without Bone Metastasis. Bone Metastasis was associated with mortality among prostate cancer patients. This association appeared to be stronger for Bone Metastasis plus SRE than for Bone Metastasis without SRE.

Shinji Miwa - One of the best experts on this subject based on the ideXlab platform.

  • tumor targeting salmonella typhimurium a1 r inhibits human prostate cancer experimental Bone Metastasis in mouse models
    Oncotarget, 2015
    Co-Authors: Makoto Toneri, Shinji Miwa, Yong Zhang, Cameron Hu, Shuuya Yano, Yasunori Matsumoto, Michael Bouvet, Hayao Nakanishi, Robert M Hoffman, Ming Zhao
    Abstract:

    Bone Metastasis is a frequent occurrence in prostate cancer patients and often is lethal. Zoledronic acid (ZOL) is often used for Bone Metastasis with limited efficacy. More effective models and treatment methods are required to improve the outcome of prostate cancer patients. In the present study, the effects of tumor-targeting Salmonella typhimurium A1-R were analyzed in vitro and in vivo on prostate cancer cells and experimental Bone Metastasis. Both ZOL and S. typhimurium A1-R inhibited the growth of PC-3 cells expressing red fluorescent protien in vitro. To investigate the efficacy of S. typhimurium A1-R on prostate cancer experimental Bone Metastasis, we established models of both early and advanced stage Bone Metastasis. The mice were treated with ZOL, S. typhimurium A1-R, and combination therapy of both ZOL and S. typhimurium A1-R. ZOL and S. typhimurium A1-R inhibited the growth of solitary Bone metastases. S. typhimurium A1-R treatment significantly decreased Bone Metastasis and delayed the appearance of PC-3 Bone metastases of multiple mouse models. Additionally, S. typhimurium A1-R treatment significantly improved the overall survival of the mice with multiple Bone metastases. The results of the present study indicate that S. typhimurium A1-R is useful to prevent and inhibit prostate cancer Bone Metastasis and has potential for future clinical use in the adjuvant setting.

  • tumor targeting salmonella typhimurium a1 r prevents experimental human breast cancer Bone Metastasis in nude mice
    Oncotarget, 2014
    Co-Authors: Shinji Miwa, Yong Zhang, Yasunori Matsumoto, Shuya Yano, Fuminari Uehara, Mako Yamamoto, Yukihiko Hiroshima, Hiroaki Kimura, Katsuhiro Hayashi, Norio Yamamoto
    Abstract:

    Bone Metastasis is a lethal and morbid late stage of breast cancer that is currently treatment resistant. More effective mouse models and treatment are necessary. High Bone-metastatic variants of human breast cancer cells were selected in nude mice by cardiac injection. After cardiac injection of a high Bone-metastatic variant of breast cancer, all untreated mice had Bone metastases compared to only 20% with parental cells. Treatment with tumor-targeting Salmonella typhimurium A1-R completely prevented the appearance of Bone Metastasis of the high metastatic variant in nude mice (P < 0.001). After injection of the highly Bone-metastatic breast cancer variant to the tibia of nude mice, S. typhimurium A1-R treatment significantly reduced tumor growth in the Bone (P < 0.001). These data indicated that S. typhimurium A1-R is useful to prevent and inhibit breast cancer Bone Metastasis and should be of future clinical use for breast cancer in the adjuvant setting.