Expression of epithelial marker CK19 in mice with mammary adenocarcinoma afterexposure to fito-anti-estrogen secoisolariciresinol

Abstract

Introduction.Phyto-anti-estrogen secoisolariciresinol (SECO) has similar effectiveness to that of Tamoxifen (TAM), a member of selection estrogen receptor modulators, in estrogen-positive models of murine mammary adenocarcinoma and human breast cancer in vivo. Due to its antagonistic and agonistic functions Tamoxifen may enhance risk of development of uterine adenocarcinoma while providing effective prophylactics of breast cancer metastases. SECO effect on proliferative activity of circulating or disseminating tumor cells (occult metastases) is still unclear. We used epithelial cell marker – intracellular cytokeratin 19 (CK19) to study SECO function in terms of possible metastatic process, since prognostic significance of CK19 is well established for identifying occult metastases and breast cancer dissemination.Objective.To evaluate risk of tumor cell dissemination in mice with transplanted mammary adenocarcinoma after exposure to SECO and TAM.Materials and methods.Mice BDF 1 [C57Bl6j × DBA2] bearing Са755 of the 3rd passage were used for the experiments. CK19 expression was evaluated 24 hours after 10-day course of SECO in the effective single doses of 250 mg/kg or ТАM 50 mg/kg. Flow cytometry, immunofluorescence with light and luminescence microscopy were performed to evaluate CK19 expression.Results.Parameter GMFI ± SD (geometric mean fluorescence intensity ± SD) for CK19 expression in SECO and TAM groups in blood accounted for 28.87 ± 13.70 and 28.02 ± 9.50 and in control tumor growth (CTG) group GMFI ± SD was 31.94 ± 5.02; while in bone marrow it was 30.14 ± 2.33, 39.07 ± 2.30 and 32.48 ± 3.75, respectively.Conclusion.The results of the study showed similar expression of epithelial intracellular marker CK19 in blood in the studied groups of mice bearing mammary adenocarcinoma Ca755 sensitive to SECO and TAM exposure. GMFI for CK19 expression in bone marrow was lower in SECO group than in TAM (р = 0.0003). The data obtained in the murine model demonstrated no enhanced risk of tumor cell dissemination while performing treatment by phyto-anti-estrogen SECO in therapeutic regimen.