Interleukin-8 Differentially Regulates Migration of Tumor-Associated and Normal Human Brain Endothelial Cells

Charalambous, Christiana; Pen, Ligaya; Su, Yuzhuang S.; Milan, Johanna; Chen, Thomas C.; Hofman, Florence M.

doi:10.1158/0008-5472.can-05-0949

Cited by 58 publications

(53 citation statements)

References 44 publications

(57 reference statements)

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“…ELR-CXC chemokine expression could play an important role in tumor microenvironment modifications (Brat et al 2005;Charalambous et al 2005). Moreover, a previous study showed increased expression of CXCL8 in advanced cancers, which could provide an important therapeutic approach for aggressive and metastatic tumors .…”

Section: Discussionmentioning

confidence: 98%

“…Indeed, increased expression of ELR-CXC chemokines and their receptors has been observed in many different cancer cells, including tumor-infiltrating neutrophils, tumor-associated macrophages and endothelial cells (Brat et al 2005;Charalambous et al 2005). ELR-CXC chemokine expression could play an important role in tumor microenvironment modifications (Brat et al 2005;Charalambous et al 2005).…”

Section: Discussionmentioning

confidence: 99%

“…CXCL8 and the two CXCL8 receptors are expressed in prostate cancer tissues (Murphy et al 2005). Furthermore, among the ELR-CXC chemokines, CXCL1-3 [growth-related oncogene (GRO)-α, -β, and -γ] are highly expressed in colon cancer cells (Doll et al 2010) and also in tumor-infiltrating neutrophils, tumor-associated macrophages, and endothelial cells, suggesting that multiple ELR-CXC chemokines can regulate the tumor microenvironment (Brat et al 2005;Charalambous et al 2005). Clinical studies have confirmed the increased expression of CXCL8 in the more advanced stages of cancers, which indicates that suppression of ELR-CXC chemokine activity may be an important therapeutic approach for aggressive and metastatic tumors .…”

mentioning

confidence: 99%

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G31P, an Antagonist against CXC Chemokine Receptors 1 and 2, Inhibits Growth of Human Prostate Cancer Cells in Nude Mice

Liu

Peng

Sun

et al. 2012

Tohoku J. Exp. Med.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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G31P, an Antagonist against CXC Chemokine Receptors 1 and 2, Inhibits Growth of Human Prostate Cancer Cells in Nude Mice

Liu

Peng

Sun

et al. 2012

Tohoku J. Exp. Med.

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“…Further, we utilize tumor microvasculature instead of the commonly used HUVECs. We and others have shown that these 2 cell types show significant differences with respect to their phenotype 14 (Fig. 4b).…”

Section: Resultsmentioning

confidence: 62%

“…Glioblastoma-derived tumor microvascular endothelial cells (tMVECs) were purified essentially as described 14 with some modifications. Initially, the glioblastoma specimens were digested in 1 mg/ml Liberase-1 (Roche) for 10 min at room-temperature.…”

Section: Co-purification Of Tumor Microvascular Endothelial Cells Andmentioning

confidence: 99%

Tumor microvasculature supports proliferation and expansion of glioma‐propagating cells

Borovski

Verhoeff

Cate

et al. 2009

Intl Journal of Cancer

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Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. The identification of 'cancer stem cellsÕ (CSC) has shed new light on the potential mechanism of therapy resistance of these tumors. Because these cells appear to be more resistant to conventional treatments, they are thought to drive tumor regrowth after therapy. Therefore, novel therapeutic approaches that target these cells are needed. Tumor cells interact with their microenvironment. It has been reported that close contact between CSCs and tumor microvascular endothelium in GBM is important for CSCs to preserve their undifferentiated state and self-renewal ability. However, our understanding of this interaction is still rudimentary. This is in part due to a lack of suitable in vitro models that accurately represent the in vivo situation. Therefore, we set up a co-culture system consisting of primary brain tumor microvascular endothelial cells (tMVECs) and glioma propagating cells (GPCs) derived from biopsies of GBM patients. We found that tMVECs support the growth of GPCs resulting in higher proliferation rates comparing to GPCs cultured alone. This effect was dependent on direct contact between the 2 cell types. In contrast to GPCs, the FCS-cultured cell line U87 was stimulated by culturing on tMVEC-derived ECM alone, suggesting that both cell types interact different with their microenvironment. Together, these results demonstrate the feasibility and utility of our system to model the interaction of GPCs with their microenvironment. Identification of molecules that mediate this interaction could provide novel targets for directed therapy for GBM. ' 2009 UICC

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Selective upregulation of interleukin‐8 by human rhabdomyosarcomas in response to hypoxia: therapeutic implications

Wysoczynski

Shin

Kucia

et al. 2009

Intl Journal of Cancer

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Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of adolescence and childhood. Because RMS tumors are highly vascularized, we sought to determine which factors secreted by RMS cells are crucial in stimulating angiogenesis in response to hypoxia. To address this issue, we evaluated expression of several proangiogenic factors [interleukin (IL)-8, vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)-2, stromal-derived factor (SDF)-1, hepatocyte growth factor (HGF), and leukemia inhibitory factor (LIF)] in 8 human RMS cell lines in both normal steady-state and hypoxic conditions. We found by real-time quantitative polymerase chain reaction (RQ-PCR) and confirmed by enzyme-linked immunosorbent assay (ELISA) that from all the factors evaluated, IL-8, whose expression is very low in normoxia, had been very highly expressed and secreted by RMS cells lines during hypoxic conditions (~40–170 times). Interestingly, this upregulation was not affected by knocking down hypoxia-inducible factor (HIF)-1α, but was inhibited by mitogen-activated protein kinase (MAPK)p42/44 and phosphatidylinositaol 3-kinase (PI3K)/AKT pathway inhibitors. This suggests that IL-8 expression is regulated in an activating protein (AP)-1- and nuclear factor (NF)-κB-dependent manner. Furthermore, we found that conditioned media (CM) harvested from RMS cells exposed to hypoxia activated and stimulated chemotactic responses in human umbilical vein endothelial cells (HUVECs) and that IL-8 was responsible for hypoxia-related effects. Finally, by employing shRNA, the expression of IL-8 in human RH-30 cells was downregulated. We noticed that such RMS cells, if injected into skeletal muscles of immunodeficient mice, have a reduced ability for tumor formation. We conclude that IL-8 is a pivotal pro-angiogenic factor released by human RMS cells in hypoxic conditions and that the targeting of IL-8 may prove to be a novel and efficient strategy for inhibiting RMS growth.

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Interleukin-8 Differentially Regulates Migration of Tumor-Associated and Normal Human Brain Endothelial Cells

Abstract: Interleukin-8 (IL-

Cited by 58 publications

References 44 publications

G31P, an Antagonist against CXC Chemokine Receptors 1 and 2, Inhibits Growth of Human Prostate Cancer Cells in Nude Mice

G31P, an Antagonist against CXC Chemokine Receptors 1 and 2, Inhibits Growth of Human Prostate Cancer Cells in Nude Mice

Tumor microvasculature supports proliferation and expansion of glioma‐propagating cells

Selective upregulation of interleukin‐8 by human rhabdomyosarcomas in response to hypoxia: therapeutic implications

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