Biological role and potential therapeutic targeting of the chemokine receptor CXCR4 in undifferentiated thyroid cancer

Valentina De Falco, Valentina Guarino, Elvira Avilla, Maria Domenica Castellone, Paolo Salerno, Giuliana Salvatore, Pinuccia Faviana, Fulvio Basolo, Massimo Santoro, Rosa Marina Melillo

Research output: Contribution to journalArticle

Abstract

Anaplastic thyroid carcinoma (ATC) is a rare thyroid cancer type with an extremely poor prognosis. Despite appropriate treatment, which includes surgery, radiotherapy, and chemotherapy, this cancer is invariably fatal. CXCR4 is the receptor for the stromal cell-derived factor-1 (SDF-1)/CXCL12 chemokine and it is expressed in a variety of solid tumors, including papillary thyroid carcinoma. Here, we show that ATC cell lines overexpress CXCR4, both at the level of mRNA and protein. Furthermore, we found that CXCR4 was overexpressed in ATC clinical samples, with respect to normal thyroid tissues by real-time PCR and immunohistochemistry. Treatment of ATC cells with SDF-1 induced proliferation and increase in phosphorylation of extracellular signal-regulated kinases and protein kinase B/AKT. These effects were blocked by the specific CXCR4 antagonist AMD3100 and by CXCR4 RNA interference. Moreover, AMD3100 effectively reduced tumor growth in nude mice inoculated with different ATC cells. Thus, we suggest that CXCR4 targeting is a novel potential strategy in the treatment of human ATC.

Original languageEnglish
Pages (from-to)11821-11829
Number of pages9
JournalCancer Research
Volume67
Issue number24
DOIs
Publication statusPublished - Dec 15 2007

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    De Falco, V., Guarino, V., Avilla, E., Castellone, M. D., Salerno, P., Salvatore, G., Faviana, P., Basolo, F., Santoro, M., & Melillo, R. M. (2007). Biological role and potential therapeutic targeting of the chemokine receptor CXCR4 in undifferentiated thyroid cancer. Cancer Research, 67(24), 11821-11829. https://doi.org/10.1158/0008-5472.CAN-07-0899