Xenotransplantation of Human Adipose Tissue in SCID Mice: a Model to Study Proximal Interactions between Adipose Tissue and Tumors

Author(s): Beaumel S, Geneste A, Duong MN, Jordheim LP, Delay E, Valet P, Perrial E, Dumontet C

The relationship between adipose tissue and cancer has been largely investigated and can be considered both in the context of obesity (endocrine effect of adipose tissue on tumors) and the interaction between juxta-tumoral adipose tissue and tumors (paracrine effect). Murine models are often used as in vivo models to study obesity, its complications as well as the impact on tumor growth. However, the direct proximity of adipose tissue and tumor has not yet been modelized in murine models. In the present project, we aimed to describe and characterize a mouse model in which xenotransplanted human abdominal adipose tissue and human breast tumors are in direct contact. We evaluated the stability of the implanted adipose tissue and functionality of the implanted tissue. We used several approaches to analyze our model at immuno-histological, cytological, protein and genetic levels on the explanted adipose tissue as well as its secretome. We also evaluated the growth of tumors in contact with adipose tissue for three breast tumor types. We found that human adipose tissue xenografts are stable in mice up to 90 days after transplantation. The quantity of adipocyte precursors remained steady in these xenografts and lipolytic function persisted up to 90 days of implantation, as evidenced by the expression levels of genes involved in lipolysis as well as by the secretion of adipokines. Growth of human breast xenografts was unaffected for MDA-MB-231 and MDA-MB-436 models while the growth of BT474 tumors was reduced by the presence of proximal adipose tissue. Sensitivity of MDA-MB-436 xenografts to doxorubicin was reduced by the presence of proximal adipose tissue. Our model is relevant and exploitable to study the proximal impact of adipose tissue on tumor growth and sensitivity to treatment.