Background: Cancer-related inflammation is recognized as a driver for tumor
progression and chemokines are important players in both inflammation and the
progression of many cancer types. CXC chemokines, especially CXCL8, have been
implicated in melanoma growth and metastasis, while less is known for their roles in drug
Methods: We generated drug-resistant cells by continuous exposure to
chemotherapeutic drugs and analyzed the mechanism(s) of therapy resistance in
Results: We report chemotherapies induced upregulation of a variety of chemokines in
the CXCR1/CXCR2 network by an NF-κB-dependent mechanism. Notably, analysis of
the drug-resistant melanoma cell line selected after prolonged exposure to
chemotherapeutic drug dacarbazine revealed higher levels of CXCL8 and CXCR2
compared with parent cells as a signature of drug resistance. CXCR2 neutralization
markedly improved sensitivity to dacarbazine in melanoma cells.
Conclusion: These data provide insights into what drives melanoma cells to survive
after chemotherapy treatment, thus pointing to strategies for developing combined drug
therapies for combating the problem of chemotherapy resistance in melanoma.