Influence of chronic neuropathic pain on VEGFA in tumors of mice with genetically determined inhibition of tumor growth.

Abstract

e22103 Background: Chronic neuropathic pain (CNP) demonstrates the ability to stimulate tumor growth and neoangiogenesis. Our purpose was to study VEGFA levels in the growth of B16/F10 melanoma with CNP in mice with genetically determined inhibition of tumor growth. Methods: Females of С57ВL/6 mice (normal genome (uPA+), n = 26) and C57BL/6-Plautm1.1BugThisPlauGFDhu/GFDhu mice (urokinase gene knockout (uPA–), n = 16) received subcutaneous transplantation of B16/F10 melanoma 2 weeks after bilateral sciatic nerve ligation (CNP model). After 3 weeks of carcinogenesis in CNP, tumor volumes were measured and levels of VEGFA were studied in tumors by ELISA. Results: Tumor volumes in (uPA+) females with CNP in week 3 of carcinogenesis were similar to that in (uPA+) females without CNP and were on average 2.6 cm3 (2.5 and 2.8 cm3 respectively). Tumor volumes in (uPA–) females were 0.04 cm3, i.e. 70 times lower (p < 0.001) than in (uPA+) females without CNP. Tumor volumes in (uPA–) females with CNP were 144 times higher (p < 0.001) than in (uPA–) females without CNP and were 5.76 cm3. VEGFA levels in tumors of (uPA+) females with CNP were 11.1 times higher (p < 0.001) than in (uPA+) females without CNP. VEGFA in tumors of (uPA–) females with CNP was 5.2 times higher (p < 0.001) than in (uPA–) females without CNP. Conclusions: The CNP state showed higher VEGFA concentrations in tumor tissues of female mice with normal genome and uPA-deficient females (with genetically determined inhibition of tumor growth) which may cause a larger tumor volume in (uPA–) female mice.