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Chronic Inflammation and Breast Cancer Recurrence

Division of Hematology-Oncology, Department of Medicine
Journal of Clinical Oncology (Impact Factor: 18.43). 06/2009; 27(21):3418-9. DOI: 10.1200/JCO.2009.21.9782
Source: PubMed
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    • "Indeed, epidemiological studies have shown that chronic inflammation predisposes individuals to various types of cancer including breast cancer, and underlying inflammatory responses are linked to 15–20% of all deaths from cancer worldwide (Mantovani et al., 2008). In addition, chronic inflammation is reported to be associated with recurrence of breast cancer (Cole, 2009). Moreover, cancer treatments are potential inducers of inflammation. "
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    ABSTRACT: Over two-thirds of the 11.4 million cancer survivors in the United States can expect long-term survival, with many others living with cancer as a chronic disease controlled by ongoing therapy. However, behavioral co-morbidities often arise during treatment and persist long-term to complicate survival and reduce quality of life. In this review, the inter-relationships between cancer, depression, and sleep disturbance are described, with a focus on the role of sleep disturbance as a risk factor for depression. Increasing evidence also links alterations in inflammatory biology dynamics to these long-term effects of cancer diagnosis and treatment, and the hypothesis that sleep disturbance drives inflammation, which together contribute to depression, is discussed. Better understanding of the associations between inflammation and behavioral co-morbidities has the potential to refine prediction of risk and development of strategies for the prevention and treatment of sleep disturbance and depression in cancer survivors.
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    • "Over the past decade, it has become increasingly clear that inflammation plays a major role in cancer pathogenesis (Mantovani et al., 2008). Several lines of evidence indicate that in breast cancer patients, some serum biomarkers of chronic inflammation are associated with disease recurrence (Cole 2009; Pierce et al., 2009) and that normal mammary gland involution, a widely acknowledged pro-tumorigenic process, is an inflammatory phenomenon (O'Brien and Schedin, 2009). Consistent with human evidence, mice models clearly indicate that inflammatory molecules released by resident immune cells or secreted systemically, are permissive for tumor development in cancer prone strains (Rao et al., 2006; O'Brien and Schedin, 2009). "
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    ABSTRACT: Extracellular and intracellular mediators of inflammation, such as tumor necrosis factor alpha (TNFα) and NF-kappaB (NF-κB), play major roles in breast cancer pathogenesis, progression and relapse. SLUG, a mediator of the epithelial-mesenchymal transition process, is over-expressed in CD44(+)/CD24(-) tumor initiating breast cancer cells and in basal-like carcinoma, a subtype of aggressive breast cancer endowed with a stem cell-like gene expression profile. Cancer stem cells also over-express members of the pro-inflammatory NF-κB network, but their functional relationship with SLUG expression in breast cancer cells remains unclear. Here, we show that TNFα treatment of human breast cancer cells up-regulates SLUG with a dependency on canonical NF-κB/HIF1α signaling, which is strongly enhanced by p53 inactivation. Moreover, SLUG up-regulation engenders breast cancer cells with stem cell-like properties including enhanced expression of CD44 and Jagged-1 in conjunction with estrogen receptor alpha down-regulation, growth as mammospheres, and extracellular matrix invasiveness. Our results reveal a molecular mechanism whereby TNFα, a major pro-inflammatory cytokine, imparts breast cancer cells with stem cell-like features, which are connected to increased tumor aggressiveness.
    Journal of Cellular Physiology 12/2010; 225(3):682-91. DOI:10.1002/jcp.22264 · 3.87 Impact Factor
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    • "Over the past decade, it has become increasingly clear that inflammation plays a major role in cancer pathogenesis (Mantovani et al., 2008). Several lines of evidence indicate that in breast cancer patients, some serum biomarkers of chronic inflammation are associated with disease recurrence (Cole 2009; Pierce et al., 2009) and that normal mammary gland involution, a widely acknowledged pro-tumorigenic process, is an inflammatory phenomenon (O'Brien and Schedin, 2009). Consistent with human evidence, mice models clearly indicate that inflammatory molecules released by resident immune cells or secreted systemically, are permissive for tumor development in cancer prone strains (Rao et al., 2006; O'Brien and Schedin, 2009). "
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    ABSTRACT: Extracellular and intracellular mediators of inflammation, such as tumor necrosis factor alpha (TNFa) and NF-kappaB (NF-kB), play major roles in breast cancer pathogenesis, progression and relapse. SLUG, a mediator of the epithelial–mesenchymal transition process, is over-expressed in CD44 þ /CD24 À tumor initiating breast cancer cells and in basal-like carcinoma, a subtype of aggressive breast cancer endowed with a stem cell-like gene expression profile. Cancer stem cells also over-express members of the pro-inflammatory NF-kB network, but their functional relationship with SLUG expression in breast cancer cells remains unclear. Here, we show that TNFa treatment of human breast cancer cells up-regulates SLUG with a dependency on canonical NF-kB/HIF1a signaling, which is strongly enhanced by p53 inactivation. Moreover, SLUG up-regulation engenders breast cancer cells with stem cell-like properties including enhanced expression of CD44 and Jagged-1 in conjunction with estrogen receptor alpha down-regulation, growth as mammospheres, and extracellular matrix invasiveness. Our results reveal a molecular mechanism whereby TNFa, a major pro-inflammatory cytokine, imparts breast cancer cells with stem cell-like features, which are connected to increased tumor aggressiveness. J. Cell. Physiol. 225: 682–691, 2010. ß 2010 Wiley-Liss, Inc. Over the past decade, it has become increasingly clear that inflammation plays a major role in cancer pathogenesis (Mantovani et al., 2008). Several lines of evidence indicate that in breast cancer patients, some serum biomarkers of chronic inflammation are associated with disease recurrence (Cole 2009; Pierce et al., 2009) and that normal mammary gland involution, a widely acknowledged pro-tumorigenic process, is an inflammatory phenomenon (O'Brien and Schedin, 2009). Consistent with human evidence, mice models clearly indicate that inflammatory molecules released by resident immune cells or secreted systemically, are permissive for tumor development in cancer prone strains (Rao et al., 2006; O'Brien and Schedin, 2009). Moreover, the knock-down (KD) of extracellular and intracellular mediators of inflammation, such as tumor necrosis factor alpha (TNFa) and NF-kappaB (NF-kB), are protective with respect to chemical-induced mammary gland carcinogenesis (Cao et al., 2007; Warren et al., 2009). Further, the in vitro activation of the TNFa/NF-kB axis induces an invasive and malignant behavior in breast cancer cells (Balkwill, 2009). The phenotype and gene expression profile of a subpopulation of CD44 þ /CD24 À breast cancer cells, endowed with tumor initiating capability (referred to as breast cancer stem cells), has recently been characterized (Al-Hajj et al., 2003; Shipitsin et al., 2007; Mani et al., 2008). Such putative breast cancer stem cells over-express members of the
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