5. MOUSE TRIPLE NEGATIVE BREAST CANCER 4T1 INTRADUCTAL MODEL CHARACTERIZATION FOR FUTURE STUDIES OF T2 ACTION

SÓLIMO ALDANA, ; SCIACCA MARIANELA, ; FILKIENSZTEIN LILIAN, ; EIJAN ANA MARIA; LODILLINSKY CATALINA, ; CALLERO MARIANA

MAR DEL PLATA

Congreso; Reunion Anual de Sociedades de Biociencias SAIC-SAI-SAFIS; 2022

Breast cancer is a neoplastic disorder of the mammary gland that remains one of the leading causes for cancer-induced death among women worldwide. Breast tumorigenesis is classically studied in mice by inoculating tumor cells in the adipose compartment of the mammary gland. Alternatively, the mammary ducts, which constitute the luminal mammary gland compartment, also provide a suitable inoculation site to induce breast cancer in murine models. Previously, our group has described an N4-aryl thiosemicarbazone (T2) action on fat pad 4T1 triple negative breast cancer model and found that this compound acts as an anti-invasive and anti-metastasic agent. However, since breast microenvironments influence tumor cell progression, we search for a more suitable model to clarify this action. In order to characterize intraductal 4T1 model, injection of several numbers and growth time of 4T1 cells have been tested. After whole mount staining of the mammary glands, we could observe positive mammary ducts (tumor cells inside the duct) with 15,000 cells 7 days after injection (a.i.). Later on, the presence of infiltrating tumor foci in the surrounding stroma was observed consistent with the presence of discontinuous SMA-alpha cell layers.The incidence rate (glands with tumour/ inoculated glands) was 100%. The percentages of positive and infiltrated ducts after 7 or 14 days a.i were 30.84 ± 4% and 4.2 ± 2.1% or 14.6 ± 2.2% and 14.3 ± 6.6, respectively In order to characterize the immune infiltration in this model, we evaluated the tumor associated CD4/CD8 cells rate and we observed that it decreased from 3.87 ± 1.6 (7 days a.i.) to 1.48 ± 0.51 (7 days a.i.) at the expense of an increase in the number of CD8 cells. Although further tumor progression markers are being studied, we conclude that the intraductal 4T1 model could be used for characterization of T2 action on tumor progression making focus in inflammatory infiltrate as preclinical mouse models that mimic the complex human disease process from primary tumor growth to metastasis.