Effect of Healthy and Tumor-Associated Breast Adipose Tissue on Breast Cancer Cell Migration and Activation

Obesity is a recognized risk factor for developing breast cancer (BC), but factors involved remain unclear. We investigated if breast adipose tissue from healthy women, BRCA1/2 mutation carriers and BC patients, can stimulate BC cell line migration and activation.

adipose tissue conditioned medium (ATCM), was prepared from breast adipose tissue from healthy subjects (naïve; group 1 (n = 20)), BRCA1/2 mutation carriers (group 2 (n = 22)) and BC patients (group 3 (n = 38)). ATCM effect on migration of BC cell lines MCF-7, SK-BR-3 and MDA-MB-231 was measured with xCELLigence (ACEA Biosciences, San Diego, CA, USA) cell migration assay. Activation of migration was determined by measuring filopodia activation. Migration and filopodia activation were related to body mass index (BMI) and BC subtypes. Luminex multiplex assay was performed to examine the secretory profile of adipose tissue.

ATCM from group 1 induced migration and filopodia activation in MCF-7 and MDA-MB-231, but not in SK-BR-3. ATCM from group 2 induced filopodia activation but no migration. ATCM from group 3 induced less migration in MCF-7 than ATCM from group 1. Higher BMI was associated with increased ATCM-induced activation in MCF-7 (group 1) and MDA-MB-231 (group 2). ATCM from group 1 and 2 showed a metabolic secretory profile, whereas group 3 showed higher pro-angiogenic and inflammatory cytokines.

This study shows that breast adipose tissue from healthy women, BRCA1/2 mutation carriers and BC patients, can stimulate BC cell line migration and activation. This effect is related to BC subtype and BMI. These data improve insight in adipose tissue as factor in BC development.