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

## TL;DR

Breast fat tissue can influence cancer cell movement, with effects varying by cancer type and body weight, raising concerns about fat-based reconstruction safety.

## Contribution

The study reveals that even healthy breast fat can stimulate cancer cell migration, highlighting implications for breast reconstruction and cancer risk.

## Key findings

- Healthy breast fat tissue stimulates cancer cell migration depending on cancer type and BMI.
- Fat tissue from BRCA1/2 carriers activates filopodia but not migration in breast cancer cells.
- Higher BMI correlates with increased activation of cancer cell migration in specific subtypes.

## Abstract

Breast fat tissue was once considered as only an energy source, but it actively releases signals that can influence nearby cells. Because obesity is linked to breast cancer risk and fat is increasingly used for breast reconstruction, we studied how breast fat tissue affects breast cancer cell behavior. We examined fat tissue from healthy women, women with inherited breast cancer risk genes, and breast cancer patients, and tested how it influenced breast cancer cell movement and activation in the laboratory. Importantly, we found that even healthy breast fat tissue can stimulate cancer cell movement, depending on the cancer type and body weight. This finding is especially relevant because the use of a woman’s own fat for breast reconstruction is increasing. Our results highlight the need for continued safety evaluation of fat-based reconstruction techniques to ensure long-term oncological safety.

Background: 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. Methods: 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. Results: 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. Conclusions: 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.