Biological role and potential therapeutic targeting of the chemokine receptor CXCR4 in undifferentiated thyroid cancer.
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.
De Falco
Valentina
V
Dipartimento di Biologia e Patologia Cellulare e Molecolare c/o Istituto di Endocrinologia ed Oncologia Sperimentale del CNR G. Salvatore, Naples, Italy.
Guarino
Valentina
V
Avilla
Elvira
E
Castellone
Maria Domenica
MD
Salerno
Paolo
P
Salvatore
Giuliana
G
Faviana
Pinuccia
P
Basolo
Fulvio
F
Santoro
Massimo
M
Melillo
Rosa Marina
RM
D002277:Carcinoma / Q000473:pathology; D002455:Cell Division; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D016133:Polymerase Chain Reaction; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D019718:Receptors, CXCR4 / Q000187:drug effects / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013961:Thyroid Gland / Q000502:physiology; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology*
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019718:Receptors, CXCR4