TSLP-mediated inflammatory factors production contributes to metastatic breast cancer-induced bone cancer pain in mice

Objective: Metastatic breast cancer-induced bone cancer pain (BCP) is one of the most disabling factors in patients suffering. Recent studies show thymic stromal lymphopoietin (TSLP) is a proinflammatory factor and high expression in cancer cells. Here we investigated whether and how TSLP released form breast cancer cells contributes to BCP. Methods: Braset cancer cells MDA-MB-231 were intramedullary injected into the femur to induce BCP, TSLP neutralizing antibody was intrathecally injected and pain hypersensitivity was checked by behavioral testing. The TSLP expression was knockdown by shRNA. Human TSLP, TNF-α, IL-1β, IL-6, CCL2, CXCL2 and CXCL5 in intramedullary space of the femur of rats was detected by ELISA. Results: TSLP neutralizing antibody intrathecally injection significantly reduced MDA-MB-231 cells inoculation induced persistent mechanical allodynia and heat hyperalgesia and TSLP increased. Furthermore, Persistent mechanical allodynia and heat hyperalgesia of mice models were also decreased in MDA-MB-231 cells with TSLP knockdown. Finally, some inflammatory factors, TNF-α, IL-1β, IL-6, CCL2, CXCL2 and CXCL5 were significantly elevated in the intramedullary space lavage fluid of the right femur after cancer cell inoculation, but were obviously reduced in models with neutralizing antibody of TSLP treatment and TSLP knockdown. Conclusion: TSLP-mediated inflammatory factors release contributes to the maintenance of tumoral hypersensitivity. Inhibition of the TSLP may provide a new therapy for BCP management.