Cervical cancer is often associated with
hypoxia and many kinds of
chemokines. But the relationship and role of
hypoxia and
Chemokine (C-C motif)
ligand 17 (CCL17) in
cervical cancer are still unknown. Here, we found that CCL17 was high expressed in
cervical cancer. HeLa and SiHa cells could secrete CCL17 in a time-dependent manner.
Hypoxia increased expression of CCL17
receptor (CCR4) on HeLa and SiHa cells. Treatment with recombination human CCL17 (rhCCL17) led to an elevation of cell proliferation in HeLa and SiHa cells in a dose-dependent manner. In contrast, blocking CCL17 with anti-human CCL17
neutralizing antibody (α-CCL17) played an oppose effect. However, rhCCL17 had no effect on apoptosis in
cervical cancer cells. Further analysis showed that
hypoxia promoted the proliferation of HeLa and SiHa cells, and these effects could be reversed by α-CCL17. Stimulation with the inhibitor for
c-Jun N-terminal kinase (JNK) or signal transducers and activator of transcription 5 (STAT5) signal pathway not only directly decreased the proliferation of HeLa and SiHa cells, but also abrogated the stimulatory effect of rhCCL17 on the proliferation of HeLa and SiHa cells. These results suggest that a high level of CCL17 in
cervical cancer lesions is an important regulator in the proliferation of
cervical cancer cells through JNK and STAT5 signaling pathways. In this process,
hypoxia magnifies this effect by up-regulating CCR4 expression and strengthening the interaction of CCL17/CCR4.