Reduced adipogenesis after lung tumor exosomes priming in human mesenchymal stem cells via TGFβ signaling pathway

A key feature of cancer cachexia is the loss of adipose tissue, mainly due to increased lipolysis and an impairment of adipogenesis. Recent findings have shown that cancer exosomes promoted lipolysis in adipose tissue. However, effects of cancer exosomes on adipogenesis were not reported. In this study, we found that lung cancer exosomes could be internalized by human adipose tissue-derived mesenchymal stem cells (hAD-MSCs) and significantly inhibited hAD-MSC adipogenesis as demonstrated by Oil Red O staining and decreased expression of adipogenic-specific genes. Specifically, TGFβ signaling pathway was demonstrated to be involved in the inhibitive effects of lung cancer exosomes on hAD-MSC adipogenesis. Additionally, TGFβ was detected in A549 exosomes. Herein, this study reports that the effect of lung cancer cell exosomes on hAD-MSC adipogenic differentiation was mediated by TGFβ signaling pathway and suggests the involvement of cancer exosomes in weight loss of cancer cachexia.