C-X-C ligand (CXCL) chemokines exert major roles in the biologic aggressiveness of esophageal cancer. In the current study, the authors investigated temozolomide (TMZ)-induced effects on activity of the CXCL chemokine network in human esophageal cancer cells. To the authors' knowledge, TMZ has not been investigated previously in experimental or clinical esophageal cancers.
A complete mapping of CXCL chemokines and their receptor messenger RNA was performed in 2 established human esophageal cancer cell lines (OE21 and OE33) and in 4 surgical samples from patients with esophageal carcinoma. The analyses pointed out the potential importance of CXCL2, and monitoring CXCL2 with quantitative videomicroscopy indicated that its biologic activity was silenced in OE21 esophageal cancer cells. TMZ-mediated antitumor activity was determined in vivo in an OE21 metastatic nude mice xenograft model.
The messenger RNA levels of CXC chemokines and their receptors were similar in both cell lines and in the 4 surgical specimens. CXCL2 depletion by small interfering RNA (siRNA) displayed marked effects on the proliferation of transfected OE21 cells. Chronic in vitro TMZ treatment of OE21 and OE33 cells markedly decreased CXCL2 and CXCL3 secretion. In vivo, TMZ induced significant delays in OE21 xenograft tumor development and improved the survival of OE21 xenograft-bearing mice, whereas cisplatin did not. Analyses performed on tissue samples from in vivo experiments revealed that TMZ also impaired tumor angiogenesis.
The current study emphasized the role of proangiogenic chemokines in esophageal cancer biology and indicated the possibility of using TMZ as a clinically compatible drug to impair the actions of the CXCL chemokine network in esophageal cancers. Cancer 2011. © 2010 American Cancer Society.