9. Development of a new breast cancer mouse model to study mechanisms involved in the in situ to invasive transition.

SCIACCA, M.; ZAMBRANO, M. ; BELGOROSKY, D. ; LANGLE, Y. ; BALARINO, N.; E. SANDES; ANA MARIA EIJAN; LODILLINSY, C.

CIUDAD AUTONOMA DE BUENOS AIRES

Congreso; Reunión Conjunta de Sociedades Biomédicas; 2017

SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA

The transition of ductal carcinoma in situ (DCIS) to invasive breast carcinoma requires tumor cells to cross the basement membrane (BM). However, mechanisms underlying BM transmigration are poorly understood. Although there are currently several mouse models with different characteristics, none have been entirely successful in understanding tumor progression in particular in the early stages. The cellular model LM38 consists in three cell lines: LM38-LP (luminal and myoepithelial), LM38-HP (luminal) and the LM38-D2 (myoepithelial).The development of a tumor model of intraductal growth using the LM38 cell lines is proposed, evaluating the behavior regarding the degree of invasion and the interactions between each of the cellular components that form the tumor.8- to 10-week old virgin female BALB/c mice were anesthetized, nipples of both inguinal glands #4 were snipped and 2 μl of cell suspension containing 2x103 cells/μl were injected in each gland. After intraductal injection, whole-mount and histology staining revealed that in glands injected with HP and D2 lines, no tumor was observed at either three or six weeks after inoculation (HP: 0 positive glands out of 16 and D2: 0 positive glands out of 20). Inoculation of the bi-cellular LP cell line developed in situ tumors, 3 weeks post-intraductal injection which were surrounded by a dense belt of collagen fibers and mioepitelial cells (SMA-alpha positive stained by Immunofluoresce). DCIS tumors further progressed to invasive lesions by 5 weeks with a disrupted stromal collagen organization (LP: 21 positive glands out of 46; p