1724P - Some mechanisms of increasing malignancy of B16/F10 melanoma in female mice with chronic pain

Abstract

Background: The impact of chronic pain (CP) on the growth and development of tumors is poorly studied. However, one of the main goals of cancer therapy is the relief of chronic pain, a complex symptom based on combined pathophysiological mechanisms. Our aim was to study the influence of CP on melanoma growth in female mice and to determine levels of the VEGF family members in the tumor (T), its perifocal zone (PZ) and in the skin. Methods: The study included 64 female C57BL/6 mice; B16/F10 melanoma was transplanted under the skin on the back of animals in the main group 2 weeks after sciatic nerve ligation. Mice with melanoma without CP were used as the controls. Levels of VEGFs: A, C, R1 and R3 were determined by ELISA (BenderMedSystem, Austria). Results: The life span of mice with melanoma and CP was 1.5 times shorter than the control group. Melanoma in mice with CP was more aggressive, and metastases occurred after 1 week vs. 4 weeks in the controls. The rate of metastasis was higher (100% vs. 60% in the controls); melanoma with CP spread to multiple organs and caused unusual metastases to the heart and uterus. The rapid and specific development of B16/F10 melanoma in mice with CP was accompanied by increased levels of VEGF-A, -C and -R1 in T, PZ and the skin, with their maximal accumulation in T in week 1. The VEGF-A level continued to increase in T and PZ (PZ<T) in week 2; VEGF-C and VEGF-R1 levels increased in PZ only and decreased in T and skin (T<PZ). The VEGF-A levels were equally highest in both T and PZ, while VEGF-C and VEGF-R1 content in T was higher than in the skin and higher in PZ than in T. The VEGF-R3 level increased in T of mice without CP and was higher in T than in PZ, while in mice with CP its content in T was lower than in PZ. Levels of VEGF-R1 (in all tissues) and VEGF-R3 (in the skin and PZ) decreased in mice with CP in week 3. Conclusions: CP shortened the life span of female mice with melanoma and enhanced the aggressiveness of B16/F10 melanoma metastases. The activation of angiogenesis in T and PZ can be considered as one of the mechanisms of the neoplastic progression. Legal entity responsible for the study: Rostov Research Institute of Oncology Funding: None Disclosure: All authors have declared no conflicts of interest.