Interleukin-8, but Not the Related Chemokine CXCL1, Sustains an Autocrine Circuit Necessary for the Properties and Functions of Thyroid Cancer Stem Cells

• DOI: 10.1002/stem.2492
• Publication Date: 2016-08-31T17:47:53Z
• Authors: Federica Liotti; Francesca Collina; Emanuela Pone; Lucia La Sala; Renato Franco; Nella Prevete; Rosa Marina Melillo
• Keywords: CXCL1; CXC chemokine receptors

Interleukin-8 (IL-8/CXCL8) mediates its biological effects through two receptors, CXCR1 and CXCR2. While recognizes IL-8 granulocyte chemotactic protein-2, CXCR2 binds to multiple chemokines including IL-8, CXCL1, 2 3. Both CXCL1 have been implicated in the neoplastic features of thyroid cancer (TC). Here, we assessed role autocrine circuits sustained by determining TC stem cell (TC SC) features. Using immunohistochemistry, found that epithelial cancerous, but not normal, cells stained positive for whose levels correlated with lymph-nodal metastases. We expression endogenous ELISA assays, their receptors CXCR2, flow cytometry, a panel lines. These molecules were expressed lines grown adherence, at higher also thyrospheres enriched stem-like cells. RNA interference demonstrated IL-8/CXCR1, CXCL1/CXCR2, is crucial sphere-forming, self-renewal tumor-initiating ability Accordingly, treatment potentiated stemness. identified CD34 as an IL-8-induced gene SC marker, since it was overexpressed compared adherent Moreover, required efficient sphere-forming tumorigenicity Our data indicate circuit, critical regulation SCs, unveils novel potential targets therapy yet untreatable forms TC. Stem Cells 2017;35:135-146.