AACR Annual Meeting-- Apr 18-22, 2009; Denver, CONasopharyngeal carcinoma (NPC), a special type of head and neck cancer occurring predominantly in areas around Southeastern China, is highly invasive and metastatic. Our previous study demonstrated that expression of chemokine receptors such as CXCR4 and CXCR6 is significantly higher in metastatic NPC tissues than primary tissues, suggesting that activation of chemokine-related signaling pathways may be involved in the metastasis of NPC. The current study was conducted to elucidate the signaling pathways related to activation of CXCR4 and CXCR6 and their reversal in NPC cells. NPC-TW01 and NPC-TW04 cells are cell lines developed from de novo NPC patients. The migration and invasion potencies of NPC cells were assessed by transwell system using modified Boyden chambers; and the activation of signaling pathways was evaluated by Western blotting using phospho-protein specific antibodies. CXCL12, the ligand of CXCR4, and CXCL16, the ligand of CXCR6, induced migration and invasion of NPC cells dose-dependently. The chemotaxis indices of CXCL12 and CXCL16 at the dose of 100 ng/ml for NPC-TW01 and NPC-TW04 were 1.8~2.0 and 1.5~2.7 (fold), respectively. NPC cells, upon treated with CXCL12 or CXCL16, responded with a prompt activation of p-ERK, followed by an increased Src autophosphorylation (Y418) and an increased p-FAK and p-paxillin. On the other hand, there were no significant changes in the expression of p-Akt in NPC cells treated with CXCL12 or CXCL16. The CXCL12 or CXCL16-induced migration of NPC cells was markedly suppressed by Src inhibitors, but was only moderately inhibited by MEK inhibitors. Our data indicated that Src and its signaling pathway play an important role in mediating the CXCR4 and CXCR6- induced migration/invasion in NPC cells. Src inhibitors, such as AZD0530, may deserve further investigation as an adjunctive therapy to prevent metastasis of NPC. (The study was supported by the grant of NSC95-2320-B-038-021-MY3.)Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2174.
|Number of pages||1|
|Issue number||9 Supplement|
|Publication status||Published - Oct 8 2014|