title: 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-13Rα2, suggesting that IL-13Rα2 mediates IL-13 effects in colorectal cancer cells. Silencing of IL-13Rα2 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-13Rα2 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-13Rα2 expression in colon cancer invasion and metastasis.
authors.affiliation: Functional Proteomics, Department of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas (CIB-CSIC), Madrid, Spain.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Barderas
authors.forename: Rubén A
authors.initials: RA
authors.lastname: Bartolomé
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Fernandez-Aceñero
authors.forename: Sofia
authors.initials: S
authors.lastname: Torres
authors.forename: J Ignacio
authors.initials: JI
authors.lastname: Casal
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D018925:Chemokines / Q000032:analysis; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology*; D006801:Humans; D018793:Interleukin-13 / Q000502:physiology; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000032:analysis / Q000502:physiology*; D008113:Liver Neoplasms / Q000556:secondary*; D051379:Mice; D009361:Neoplasm Invasiveness; D011379:Prognosis; D015398:Signal Transduction
chemical_list: D018925:Chemokines; D018793:Interleukin-13; D053663:Interleukin-13 Receptor alpha2 Subunit