Increased Serum Interleukin-8 in Patients with Early and Metastatic Breast Cancer Correlates with Early Dissemination and Survival

Benoy, Ina; Salgado, Roberto; Dam, Peter van; Geboers, Katrien; Marck, Eric Van; Scharpé, Simon; Vermeulen, Peter; Dirix, Luc

doi:10.1158/1078-0432.ccr-04-0812

Cited by 318 publications

(258 citation statements)

References 31 publications

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“…This is in concordance with the observations in patient biopsies, where these cytokines were expressed at elevated levels in basal‐like tumors compared to the luminal tumors. As these cytokines are associated with poor prognosis and cancer progression (Benoy et al ., 2004; Lv et al ., 2013; Salgado et al ., 2003), their abundance in basal‐like tumors may be linked to the aggressive behavior of this subtype. In the current study, we pursued this idea by studying the ability of BCC‐secreted factors to engage tumor‐supportive macrophages.…”

Section: Discussionmentioning

confidence: 99%

Basal‐like breast cancer engages tumor‐supportive macrophages via secreted factors induced by extracellular S100A4

et al. 2018

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The tumor microenvironment (TME) may influence both cancer progression and therapeutic response. In breast cancer, particularly in the aggressive triple‐negative/basal‐like subgroup, patient outcome is strongly associated with the tumor's inflammatory profile. Tumor‐associated macrophages (TAMs) are among the most abundant immune cells in the TME, shown to be linked to poor prognosis and therapeutic resistance. In this study, we investigated the effect of the metastasis‐ and inflammation‐associated microenvironmental factor S100A4 on breast cancer cells (BCCs) of different subtypes and explored their further interactions with myeloid cells. We demonstrated that extracellular S100A4 activates BCCs, particularly the basal‐like subtype, to elevate secretion of pro‐inflammatory cytokines. The secreted factors promoted conversion of monocytes to TAM‐like cells that exhibited protumorigenic activities: stimulated epithelial–mesenchymal transition, proliferation, chemoresistance, and motility in cancer cells. In conclusion, we have shown that extracellular S100A4 instigates a tumor‐supportive microenvironment, involving a network of cytokines and TAM‐like cells, which was particularly characteristic for basal‐like BCCs and potentiated their aggressive properties. The S100A4–BCC–TAM interaction cascade could be an important contributor to the aggressive behavior of this subtype and should be further explored for therapeutic targeting.

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Section: Discussionmentioning

confidence: 99%

Basal‐like breast cancer engages tumor‐supportive macrophages via secreted factors induced by extracellular S100A4

et al. 2018

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“…In an experimental model of ovarian cancer, the expression of CXCL8 was directly correlated with neovascularization and poor survival [86]. CXCL8 may also play an important role in angiogenesis in prostate and breast cancer as serum levels of CXCL8 are elevated in patients with prostate and breast cancer, and correlate with disease stage [87][88][89][90][91]. The ability of CXCL8 to elicit angiogenic activity depends on the expression of its receptor by endothelial cells.…”

Section: Chemokines In Angiogenesismentioning

confidence: 99%

Chemokines in tumor angiogenesis and metastasis

Singh

Sadanandam

Singh

2007

Cancer Metastasis Rev

158

132

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Chemokines are a large group of low molecular weight cytokines that are known to selectively attract and activate different cell types. Although the primary function of chemokines is well recognized as leukocyte attractants, recent evidences indicate that they also play a role in number of tumor-related processes, such as growth, angiogenesis and metastasis. Chemokines activate cells through cell surface seven trans-membranes, G-protein-coupled receptors (GPCR). The role played by chemokines and their receptors in tumor pathophysiology is complex as some chemokines favor tumor growth and metastasis, while others may enhance anti-tumor immunity. These diverse functions of chemokines establish them as key mediators between the tumor cells and their microenvironment and play critical role in tumor progression and metastasis. In this review, we present some of the recent advances in chemokine research with special emphasis on its role in tumor angiogenesis and metastasis.

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“…IL-8 was subsequently found to promote the growth and metastasis of tumors, in part by stimulating angiogenesis (Green et al, 1997;Bar-Eli, 1999;De Larco et al, 2001;Rofstad and halsor, 2002;Chen et al, 2003;Freund et al, 2003;Benoy et al, 2004). Both tumor cells and tumorassociated neutrophils and macrophages have been reported to release IL-8, which contributes to accelerated tumor growth and poor survival (Chen et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…IL-8 overexpression is associated with high metastatic potential in breast cancers (Green et al, 1997;De Larco et al, 2001;Freund et al, 2003). IL-8 serum levels are increased in patients with breast cancers and are an independent prognostic factor for survival (Benoy et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

HER2 signaling modulates the equilibrium between pro- and antiangiogenic factors via distinct pathways: implications for HER2-targeted antibody therapy

et al. 2006

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We determined the impact of HER2 signaling on two proangiogenic factors, vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8), and on an antiangiogenic factor, thrombospondin-1 (TSP-1). Re-expression of HER2 in MCF-7 and T-47D breast cancer cells that endogenously express low levels of HER2 resulted in elevated expression of VEGF and IL-8 and decreased expression of TSP-1. Inhibition of HER2 with a humanized anti-HER2 antibody (trastuzumab, or Herceptin s ) or a retrovirus-mediated small interfering RNA against HER2 (siHER2) decreased VEGF and IL-8 expression, but increased TSP-1 expression in BT474 breast cancer cells that express high levels of HER2. These in vitro results were further evaluated by treatment of BT474 xenografts in immunosuppressed mice with trastuzumab. Trastuzumab inhibited growth of BT474 xenografts and decreased microvascular density associated with downregulation of VEGF and IL-8 and with upregulation of TSP-1 expression. Inhibiting the PI3K-AKT pathway decreased VEGF and IL-8 expression. AKT1 overexpession increased VEGF and IL-8 expression, but did not increase TSP-1 expression. A p38 kinase inhibitor, SB203580, instead blocked TSP-1 expression and a p38 activator, MKK6, increased TSP-1 expression. Trastuzumab stimulated sustained p38 activation and SB203580 attenuated the TSP-1 upregulation induced by trastuzumab. HER2 signaling therefore influences the equilibrium between pro-and antiangiogenic factors via distinct signaling pathways. Trastuzumab inhibits angiogenesis and tumor growth, at least in part, through activation of the HER2-p38-TSP-1 pathway and inhibition of the HER2-PI3K-AKT-VEGF/IL-8 pathway.

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Increased Serum Interleukin-8 in Patients with Early and Metastatic Breast Cancer Correlates with Early Dissemination and Survival

Cited by 318 publications

References 31 publications

Basal‐like breast cancer engages tumor‐supportive macrophages via secreted factors induced by extracellular S100A4

Basal‐like breast cancer engages tumor‐supportive macrophages via secreted factors induced by extracellular S100A4

Chemokines in tumor angiogenesis and metastasis

HER2 signaling modulates the equilibrium between pro- and antiangiogenic factors via distinct pathways: implications for HER2-targeted antibody therapy

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