IL‐1 family in breast cancer: Potential interplay with leptin and other adipocytokines

Perrier, Stéphane; Caldefie-Chézet, Florence; Vasson, Marie‐Paule

doi:10.1016/j.febslet.2008.12.030

Cited by 90 publications

(64 citation statements)

References 88 publications

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“…However, the tamoxifen-induced increase in IL1b was associated with a concomitant increase in the level of IL1Ra, a natural inhibitor of IL1, to a higher extent than that of IL1b, leading to inactivation of IL1b. This is consistent with the antitumorigenic property of this cytokine that we, and others, have recently described (27,53).…”

Section: Discussionsupporting

confidence: 92%

CCL2 and CCL5 Are Novel Therapeutic Targets for Estrogen-Dependent Breast Cancer

Svensson

Abrahamsson

Rodriguez

et al. 2015

Clinical Cancer Research

186

145

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Purpose: Novel therapeutic targets of estrogen receptor (ER)-positive breast cancers are urgently needed because current antiestrogen therapy causes severe adverse effects, nearly 50% of patients are intrinsically resistant, and the majority of recurrences have maintained ER expression. We investigated the role of estrogen-dependent chemokine expression and subsequent cancer growth in human tissues and experimental breast cancer models.Experimental Design: For in vivo sampling of human chemokines, microdialysis was used in breast cancers of women or normal human breast tissue before and after tamoxifen therapy. Estrogen exposure and targeted therapies were assessed in immune competent PyMT murine breast cancer, orthotopic human breast cancers in nude mice, cell culture of cancer cells, and freshly isolated human macrophages. Cancer cell dissemination was investigated using zebrafish. Results: ERþ cancers in women produced high levels of extracellular CCL2 and CCL5 in vivo, which was associated with infiltration of tumor-associated macrophages. In experimental breast cancer, estradiol enhanced macrophage influx and angiogenesis through increased release of CCL2, CCL5, and vascular endothelial growth factor. These effects were inhibited by anti-CCL2 or anti-CCL5 therapy, which resulted in potent inhibition of cancer growth. In addition, estradiol induced a protumorigenic activation of the macrophages. In a zebrafish model, macrophages increased cancer cell dissemination via CCL2 and CCL5 in the presence of estradiol, which was inhibited with anti-CCL2 and anti-CCL5 treatment. Conclusions: Our findings shed new light on the mechanisms underlying the progression of ER þ breast cancer and indicate the potential of novel therapies targeting CCL2 and CCL5 pathways.

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Section: Discussionsupporting

confidence: 92%

CCL2 and CCL5 Are Novel Therapeutic Targets for Estrogen-Dependent Breast Cancer

Svensson

Abrahamsson

Rodriguez

et al. 2015

Clinical Cancer Research

186

145

View full text Add to dashboard Cite

show abstract

“…Several studies have reported that high IL-1b concentration within the tumor microenvironment is associated with a more virulent tumor phenotype and correlates with a higher rate of recurrence (2,35). Moreover in breast cancer patients, it has been shown that high levels of IL-1Ra and low levels of IL-1 at the tumor site is associated with a better prognosis (36) emphasizing the clinical relevance of our results. The cancer cells in our model did produce low levels of extracellular IL-1b.…”

Section: Discussionsupporting

confidence: 71%

Tamoxifen, Flaxseed, and the Lignan Enterolactone Increase Stroma- and Cancer Cell–Derived IL-1Ra and Decrease Tumor Angiogenesis in Estrogen-Dependent Breast Cancer

et al. 2011

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The proinflammatory cytokines IL-1a and IL-1b promote tumor angiogenesis that might be counteracted by the IL-1 receptor antagonist (IL-1Ra), anakinra, a clinically approved agent. A diet with high amounts of phytoestrogens, such as flaxseed (Flax), genistein (GEN), and the mammalian lignan enterolactone (ENL), may affect breast cancer progression in a similar fashion as the antiestrogen tamoxifen. Both cancer cells and tumor stroma may be targets for cancer therapy. By using microdialysis in a model of human breast cancers in nude mice, we could perform species-specific analyses of released proteins in the microenvironment. We show that tumors treated with tamoxifen and fed Flax or ENL exhibited decreased in vivo release of IL-1b derived from the murine stroma and decreased microvessel density whereas dietary GEN had no effects. Cancer cell-released IL1Ra were approximately 5 times higher than stroma-derived IL-1Ra. Tamoxifen, Flax, and ENL increased IL-1Ra levels significantly whereas GEN did not. The tumor stroma contained macrophages, which expressed the estrogen receptor. In vitro, estradiol decreased IL-1Ra released from breast cancer cells and from cultured macrophages. IL-1Ra decreased endothelial cell proliferation significantly in vitro whereas breast cancer cell proliferation was unaffected in presence of estradiol. Finally, IL-1Ra therapy of tumor-bearing mice opposed estrogen-dependent breast cancer growth and decreased angiogenesis. We conclude that the release of IL-1s both by cancer cells and the stroma, where macrophages are a key component, may offer feasible targets for antiestrogen therapy and dietary interventions against breast cancer. Cancer Res; 71(1); 51-60. Ó2011 AACR.

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“…Nevertheless, in nonneoplastic skin pathologies, several investigators have reported S100A7 induction in response to inflammatory cytokines, including OSM, IL-1, IL-17, IL-20 and IL-22 (Boniface et al, 2005;Gazel et al, 2006;Liang et al, 2006;Wolk et al, 2006;Bando et al, 2007;Boniface et al, 2007;Sa et al, 2007). Each of these cytokines has the capacity to signal, either directly or indirectly, through STAT3, ERK1/2 and PI3K (Heinrich et al, 2003;Pestka et al, 2004;Gaffen, 2008;Perrier et al, 2008). We have shown previously that S100A7 in breast tumors correlates with Akt activation (Emberley et al, 2005) and now show that OSM and IL-6 can induce S100A7 via PI3K, ERK1/2 or STAT3.…”

Section: Inflammatory Cytokines Induce S100a7 Expression In Breast Cellsmentioning

confidence: 99%

S100A7 (psoriasin) is induced by the proinflammatory cytokines oncostatin-M and interleukin-6 in human breast cancer

West

Watson

2010

Oncogene

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S100A7 promotes aggressive features in breast cancer, although regulation of its expression is poorly understood. As S100A7 associates with inflammation in skin and breast tissue, we hypothesized that inflammatory cytokines may regulate S100A7 in breast cancer. We therefore examined the effects of several cytokines, among which oncostatin-M (OSM) and the related cytokine, interleukin (IL)-6, showed the most significant effects on S100A7 expression in breast tumor cells in vitro. Both cytokines consistently induced S100A7 expression in three cell lines (MCF7, T47D and MDA-MB-468) in a dose-and time-dependent manner. Induction of S100A7 was inhibited by blockade of STAT3, phosphatidylinositol 3 kinase (PI3K) and ERK1/2 signaling and small interference RNA (siRNA)-mediated knockdown of S100A7 eliminated the promigratory effects of OSM treatment. S100A7 mRNA levels in a case-control cohort of breast tumors (n ¼ 20) were significantly associated with expression of the OSM receptor b (OSMRb) chain (P ¼ 0.0098). This association was confirmed using publicly available microarray data from an independent breast tumor cohort (n ¼ 201, P ¼ 0.0005) and a correlation between S100A7 and poor patient survival was observed specifically in cases with high OSMRb expression (HR ¼ 2.35; P ¼ 0.0396; n ¼ 85). We conclude that inflammatory cytokines can regulate S100A7 expression and that S100A7 may mediate some of their effects in breast cancer.

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IL‐1 family in breast cancer: Potential interplay with leptin and other adipocytokines

Cited by 90 publications

References 88 publications

CCL2 and CCL5 Are Novel Therapeutic Targets for Estrogen-Dependent Breast Cancer

CCL2 and CCL5 Are Novel Therapeutic Targets for Estrogen-Dependent Breast Cancer

Tamoxifen, Flaxseed, and the Lignan Enterolactone Increase Stroma- and Cancer Cell–Derived IL-1Ra and Decrease Tumor Angiogenesis in Estrogen-Dependent Breast Cancer

S100A7 (psoriasin) is induced by the proinflammatory cytokines oncostatin-M and interleukin-6 in human breast cancer

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