Large adipocytes in a biomimetic adipose tissue model promote breast cancer malignancy.
Overview
abstract
Obesity worsens breast cancer survival but how increased adipocyte size, which typifies obese adipose tissue and correlates with poor prognosis, impacts cancer progression remains unclear. Understanding these connections is challenging as adipocyte size is highly heterogeneous and not tunable with traditional experimental approaches. Here, we develop a biomimetic, engineered adipose tissue model to culture size-sorted adipocytes isolated from the same donor and assess their impact on tumor cell behavior. We find that large adipocytes are transcriptionally distinct from small adipocytes and upregulate genes related to adipose tissue dysfunction, including altered lipid processing. In coculture, large adipocytes promote lipid accumulation in cancer cells, increasing their migration and proliferation via enhanced fatty acid oxidation. These changes align with greater extracellular vesicle release by large adipocytes, which transfer lipid to recipient tumor cells. Our findings posit adipocyte size as an independent prognostic biomarker for breast cancer patients and demonstrate the value of biomimetic tissue models for mechanistic studies.
