Increased levels of interleukins 8 and 10 as findings of canine inflammatory mammary cancer

Andrés, Paloma Jimena de; Illera, Juan Carlos; Cáceres, Sara; Díez, Lucía; Alenza, María Dolores Pérez; Peña, Laura

doi:10.1016/j.vetimm.2012.12.010

Cited by 34 publications

(32 citation statements)

References 43 publications

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“…More specifically, we showed that IL-8 was highly up-regulated in canine HSA cells compared to non-malignant endothelial cells derived from splenic hematomas, suggesting that IL-8 has a crucial role in the malignancy of these tumors [17]. Recent studies also have shown that the levels of IL-8 were higher in blood obtained from dogs with mammary cancer than in blood from healthy dogs, suggesting that IL-8 may be an important prognostic serum marker [18, 19]. However, a functional role of IL-8 in spontaneous canine cancers has not been reported.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-8 promotes canine hemangiosarcoma growth by regulating the tumor microenvironment

Kim

Frantz

Anderson

et al. 2014

Experimental Cell Research

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Interleukin-8 (IL-8) gene expression is highly up-regulated in canine hemangiosarcoma (HSA); however, its role in the pathogenesis of this disease is unknown. We investigated the expression of IL-8 in canine HSA tissues and cell lines, as well and the effects of IL-8 on canine HSA in vitro, and in vivo using a mouse xenograft model for the latter. Constitutive expression of IL-8 mRNA, IL-8 protein, and IL-8 receptor were variable among different tumor samples and cell lines, but they showed stable steady states in each cell line. Upon the addition of IL-8, HSA cells showed transient intracellular calcium fluxes, suggesting that their IL-8 receptors are functional and that IL-8 binding activates relevant signaling pathways. Yet, neither addition of exogenous IL-8 nor blockade of endogenous IL-8 by neutralizing anti-IL-8 antibody (α-IL-8 Ab) affected HSA cell proliferation or survival in vitro. To assess potential effects of IL-8 in other tumor constituents, we stratified HSA cell lines and whole tumor samples into “IL-8 high” and “IL-8 low” groups. Genome-wide gene expression profiling showed that samples in the “IL-8 high” tumor group were enriched for genes associated with a “reactive microenvironment,” including activation of coagulation, inflammation, and fibrosis networks. Based on these findings, we hypothesized that the effects of IL-8 on these tumors were mostly indirect, regulating interactions with the microenvironment. This hypothesis was supported by in vivo xenograft experiments where survival and engraftment of tumor cells was inhibited by administration of neutralizing α-IL-8 Ab. Together, our results suggest that IL-8 contributes to establishing a permissive microenvironment during the early stages of tumorigenesis in HSA.

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Section: Introductionmentioning

confidence: 99%

Interleukin-8 promotes canine hemangiosarcoma growth by regulating the tumor microenvironment

Kim

Frantz

Anderson

et al. 2014

Experimental Cell Research

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“…These biomarkers are able to generate main information related to clinical manner of breast gland tumors (4). Iinterleukin-8 (IL-8) is also over-expressed in various human tumors (5,6) and increased with malignancy (7). The influence of IL-8 in migration and invasion of tumor cells is important for progression and metastasis formation of tumors (8).…”

Section: Contextmentioning

confidence: 99%

The Role of Interleukin-8 and Its Mechanism in Patients with Breast Cancer: Its Relation with Oxidative Stress and Estrogen Receptor

Sheikhpour

2017

Int J Cancer Manag

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Context: Breast cancer is one of the leading causes of death among women all over the world. Prognostic markers can be used for patient survival. Likewise, these biomarkers are able to generate main information related to clinical manner of breast gland tumors. Interleukin-8 (IL-8) is a chemotactic cytokines caused initiation of an inflammatory response. Evidence Acquisition: We performed a computerized search in Medline/PubMed databases with key words: IL-8, breast cancer, and oxidative stress. Results: IL-8 secretion motivates the expression of adhesion molecule, including fibronectin in human inflammatory breast cancer cells. IL-8 activates PI3K/Akt pathway, which in turn activates NF-κB resulted up-regulation of integrin β3 expression and increases the invasion of breast cancer cells. Therefore, it seems that IL-8/PI3K/Akt/NF-κB/integrin β3 axis may be used for therapeutic intervention of breast cancer with metastasis status. NF-κB plays an important role in IL-8 gene transcription via several signals, such as LPS, TNF-alpha, and oxidative stress. Oxidative stress caused angiogenic factor production, such as vascular endothelial growth factor and IL-8 via cancer cells. Moreover, there is inverse relation between ER level and IL-8, but the mechanism of IL-8 action in estrogen receptor-negative breast cancer is largely unknown. Estrogen receptor and growth factor in breast cancer cells is influenced by mitogen activated protein kinase (MAPK) cascade, as a part of IL-8 signaling pathway. Conclusions: According to these studies, interleukin-8 may be as a main biomarker for breast cancer. It seems that signaling pathway of IL-8 may be used for therapeutic intervention of breast cancer. Also oxidative stress and breast cancer cells with lacking estrogen receptor generate more interleukin-8.

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“…Additionally, serum CXCL8 is susceptible to changes in its concentration due to dilution and its reliability to predict local changes should therefore be questioned. Although some studies showed a congruent increase in local and systemic CXCL8 values (De Andrés et al, 2013;Tamura et al, 2013) a study by Konno et al (2003) found a relationship between CXCL8 and a variety of tumor parameters in drainage veins of gastric cancer, whereas no significant relationship in peripheral veins (Konno et al, 2003). Moreover, the producing cells as well as the function of local and systemic CXCL8 may differ so that both should be included and compared in future studies.…”

Section: Discussionmentioning

confidence: 99%

“…Although the major production of CXCL8 occurs locally as an adaptive response of cancer cells to withstand environmental or chemical stresses (Kim et al, 2014;Raman et al, 2007;Desbaillets et al, 1997;Shi et al, 2001), its concentration has been found to be also elevated in the blood of human and canine cancer patients (Yokoe et al, 1996;Ueda et al, 1994;Veltri et al, 1999;Gelaleti et al, 2012;De Andrés et al, 2013;Konno et al, 2003;Ugurel et al, 2001;Ren et al, 2003;Benoy et al, 2004;Lokshin et al, 2006). On the one hand, cells within the tumor tissue are known to secrete CXCL8 that may partly escape the tumor environment and reach the bloodstream through the vast amount of blood vessels that usually nourish a tumor.…”

Section: Discussionmentioning

confidence: 99%

“…A later study by the same group had opposite results showing a positive correlation between high serum CXCL8 values and tumor progression, lymph node involvement, metastasis, recurrence and death (Gelaleti et al, 2012). Similarly, a more recent study by De Andrés et al (2013) supported this finding by assessing local and serum CXCL8 in benign and malignant mammary gland tumors (De Andrés et al, 2013). A study by Kim et al (2014) on local CXCL8 expression in canine hemangiosarcoma suggested that the effect of CXCL8 is mostly indirect and that its production is part of an adaptive mechanism used by tumor cells to modulate their microenvironment (Kim et al, 2014).…”

Section: Introductionmentioning

confidence: 95%

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Evaluation of Serum Interleukin-8 (CXCL8) Concentrations in Tumor Bearing Dogs

Haas

Kaup

Neumann

2015

American Journal of Animal and Veterinary Sciences

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Interleukin-8 (IL-8 or CXCL8) is a pro-inflammatory and angiogenic chemokine involved in tumorigenesis. Serum CXCL8 is elevated in various neoplastic diseases, but its potential value as a tumor marker in veterinary medicine is unknown. Here, we measured serum CXCL8 concentrations in dogs with various neoplastic diseases using a commercially available canine ELISA kit and analyzed its relationship with patient and disease features. Serum CXCL8 was detected in significantly higher concentrations in tumor bearing dogs compared with healthy patients (p<0.001). Interestingly, serum CXCL8 increased with augmenting tumor size while it decreased with raising malignancy (p=0.01 and p<0.001, respectively). We found no correlation with the tumor type, tissue origin and histological features such as vascularization, necrosis or infiltrating cells. Some of the associations between CXCL8 and neoplastic features stated in human research were corroborated in this study, suggesting the need for investigating its relevance in tumor bearing dogs.

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Increased levels of interleukins 8 and 10 as findings of canine inflammatory mammary cancer

Cited by 34 publications

References 43 publications

Interleukin-8 promotes canine hemangiosarcoma growth by regulating the tumor microenvironment

Interleukin-8 promotes canine hemangiosarcoma growth by regulating the tumor microenvironment

The Role of Interleukin-8 and Its Mechanism in Patients with Breast Cancer: Its Relation with Oxidative Stress and Estrogen Receptor

Evaluation of Serum Interleukin-8 (CXCL8) Concentrations in Tumor Bearing Dogs

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