Premium
Chemokine receptors in head and neck cancer: Association with metastatic spread and regulation during chemotherapy
Author(s) -
Muller Anja,
Sonkoly Eniko,
Eulert Christine,
Gerber Peter Arne,
Kubitza Robert,
Schirlau Kerstin,
FrankenKunkel Petra,
Poremba Christopher,
Snyderman Carl,
Klotz LarsOliver,
Ruzicka Thomas,
Bier Henning,
Zlotnik Albert,
Whiteside Theresa L.,
Homey Bernhard,
Hoffmann Thomas K.
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21514
Subject(s) - chemokine receptor , ccr10 , cxcr4 , cancer research , cxc chemokine receptors , metastasis , chemokine , cc chemokine receptors , cxcl14 , biology , receptor , pathology , cancer , medicine
Head and neck carcinomas are histologically and clinically heterogeneous. While squamous cell carcinomas (SCC) are characterized by lymphogenous spread, adenoid cystic carcinomas (ACC) disseminate preferentially hematogenously. To study cellular and molecular mechanisms of organ‐specific metastasis, we used SCC and ACC cell lines and tumor tissues, obtained from patients with primary or metastatic disease. Comprehensive analysis at the mRNA and protein level of human chemokine receptors showed that SCC and ACC cells exhibited distinct and nonrandom expression profiles for these receptors. SCC predominantly expressed receptors for chemokines homeostatically expressed in lymph nodes, including CC chemokine receptor (CCR) 7 and CXC chemokine receptor (CXCR)5. No difference in expression of chemokine receptors was seen in primary SCC and corresponding lymph node metastases. In contrast to SCC, ACC cells primarily expressed CXCR4. In chemotaxis assays, ACC cells were responsive to CXCL12, the ligand for CXCR4. Exposure of ACC cells to cisplatin resulted in upregulation of CXCR4 on the cell surface, which was repressed by the transcriptional inhibitor, α‐amanitin. Treatment of ACC cells with CXCL12 resulted in the activation of Akt and ERK1/2 pathways. Furthermore, CXCL12 suppressed the rate of apoptosis induced by cisplatin in ACC cells, suggesting that signaling via CXCR4 may be part of a tumor cell survival program. Discrimination of the chemokine receptor profile in SCC and ACC in vitro and in tissues provided insights into their distinct biologic and clinical characteristics as well as indications that chemokine receptors might serve as future therapeutic targets in these malignancies. © 2005 Wiley‐Liss, Inc.