Adipose cells could favor breast cancer invasion by inducing the loss of the tumor-suppressor profile of mammary myoepithelial cells

Laetitia Delort (1) , Marion Bernard-Vermerie (1, 2) , Caroline Decombat (1, 2) , Ali Mojallal (3, 4) , Céline Auxenfans (3, 4) , Florence Caldefie-Chezet (1)

1 UNH - Unité de Nutrition Humaine
2 UCA [2017-2020] - Université Clermont Auvergne [2017-2020]
3 service de chirurgie plastique, reconstructrice et esthétique
4 HCL - Hospices Civils de Lyon

Obesity is responsible for higher recurrence and mortality breast cancer (BC) rates. Of all the cell types present in the breast, myoepithelial cells (MyoEpCs) are considered "tumor suppressors". During the transition from in situ to invasive ductal BC, a disorganization of MyoEpCs is observed that promotes the ability of cancer cells to migrate. As the adipose microenvironment could promote BC, we would like to characterize its role on the functionality of MyoEpCs in an obese context. For this purpose, MyoEpCs (Hs 578Bst) were co-cultured with human adipose stem cells (hASC) (hMAD cell line and hASCs from healthy women). We found that the viability of MyoEpCs was reduced in the presence of hASC (-23%, -10% with hMAD and hASC respectively, p<0.05) associated with a slight increase in apoptosis. When hASC were differentiated into mature adipocytes (MA), the same impact on viability was observed (-11%, p<0.01). The influence of obesity was evaluated using hASC from thin or obese patients (hASC20, hASC30) differentiated into MA (MA20, MA30). Cells of obese women had slightly less activity on MyoEpCs viability (-13% with hASC20; -8% with hASC30; -16% with MA20, p<0.01; -8% with MA30, ns). Adipose secretome alone had less important effects on MyoEpCs, highlighting the importance of cell-cell interactions. MyoEpCs co-cultured with MA expressed significantly less AdipoR1 (RQ=0.7) and CDH1 (RQ=0.3), suggesting a loss of functionality of MyoEpCs. In addition, an increase in the expression of genes normally poorly or not expressed by MyoEpCs was observed. These preliminary results confirmed that adipose cells and their secretome could influence the behavior of MyoEpCs and lead to the loss of the "tumor suppressor" status. A 3D organoids model is being developed to evaluate the influence of adipose secretome on the structure and functionality of MyoEpCs and will identify new preventive and therapeutic targets for BC.

Mots clés: breast cancer; myopiepithelial cells; adipocytes

Domaines: Alimentation et Nutrition

Laetitia Delort, Marion Bernard-Vermerie, Caroline Decombat, Ali Mojallal, Céline Auxenfans, et al.. Adipose cells could favor breast cancer invasion by inducing the loss of the tumor-suppressor profile of mammary myoepithelial cells. Forum de la Recherche en Cancérologie Rhône-Alpes Auvergne, Apr 2019, Lyon, France. 2019. ⟨hal-02073384⟩