High Expression of IL-13 Receptor α2 in Colorectal Cancer Is Associated with Invasion, Liver Metastasis, and Poor Prognosis

Abstract

Autocrine secretion of cytokines by metastatic colorectal cancer cells and their role during invasion and liver homing has been poorly characterized. In this study, we used cytokine arrays to analyze the secretomes of poorly and highly metastatic colorectal cancer cells. Compared with poorly metastatic cancer cells, highly metastatic cells expressed increased levels of the immunosuppressive cytokines interleukin (IL)-4 and IL-13 in addition to increased surface expression of the high affinity IL-13 receptor IL-13Ra2, suggesting that IL-13Ra2 mediates IL-13 effects in colorectal cancer cells. Silencing of IL-13Ra2 in highly metastatic cells led to a decrease in adhesion capacity in vitro and a reduction in liver homing and increased survival in vivo, revealing a role for this receptor in cell adhesion, migration, invasion, and metastatic colonization. In support of this, IL-13 signaling activated the oncogenic signaling molecules phosphoinositide 3-kinase, AKT, and SRC in highly metastatic cells. Clinically, high expression of IL-13Ra2 was associated with later stages of disease progression and poor outcome in patients with colorectal cancer. Our findings therefore support a critical role for IL-13Ra2 expression in colon cancer invasion and metastasis. Cancer Res; 72(11); 2780-90. Ó2012 AACR.

A Proteomic Analysis Reveals That Snail Regulates the Expression of the Nuclear Orphan Receptor Nuclear Receptor Subfamily 2 Group F Member 6 (Nr2f6) and Interleukin 17 (IL-17) to Inhibit Adipocyte Differentiation *

“…Then, membranes were scanned and analyzed using Redfin, a 2D-gel image analysis software (Ludesi, Malmoe, Sweden) as described (23). Relative cytokine intensities were normalized in comparison to control spots on the same membrane and represented in arbitrary units.…”

An RGD Motif Present in Cadherin 17 Induces Integrin Activation and Tumor Growth

“…The Ethical Committee of the Consejo Superior de Investigaciones Científicas (Madrid, Spain) approved the protocols used for experimental work with mice. Liver homing assays were performed as described previously (17). Briefly, 10 6 cells, KM12SM or RKO, transfected with vectors encoding for CDH17 WT, RAD, or empty vectors (mock) were inoculated intrasplenically into mice (n ϭ 3), which were euthanized after 24 h. RNA was isolated from mouse livers using TRIzol and retrotranscribed.…”

Effect of chromium disilicide and titanium nitride nanoparticles on the expression of NAMPT, E2F8, FAS, TBX3, IL13RA2, and UPS7 genes in mouse liver

“…There is data that organic extraction from drinking water impairs liver function with the involvement of death receptor FAS and mitochondria-mediated apoptosis in rats [14]. Interleukin 13 receptor, α2 (IL13RA2) has high affinity to interleukin-13 and highly expressed in colorectal cancer, glioblastoma and other malignant tumors, is associated with invasion and liver metastasis [15,16]. Moreover, low-dose cadmium has growth-promoting effects on NPrEC cells and induces transient overexpression of genes with oncogenic and immunomodulation functions, including TNF and Il13ra2 [17].…”

“…In this work, we studied the effect of titanium nitride and chromium disilicide nanoparticles on the expression of a subset of genes encoding different regulatory enzymes, receptors and transcription factors, which play an important role in various metabolic pathways and thus control proliferation and apoptosis [9,12,14,15,18,22,25]. For titanium dioxide nanoparticles, which are widely used in the number of applications, including cosmetic creams, toothpastes, and component of surgical implants, it was shown that long-term exposure to these nanoparticles led to accumulation of these nanoparticles in brain, over-proliferation of glial cells and significant changes in brain gene expressions as well as to neurogenic disease states in mice [1,2].…”

“…It is well known that proteins encoded by all these genes play an important role in controlling apoptosis, cell proliferation, and cancer growth [9,12,15,22]. As shown in Fig.…”