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We read with great interest the recent publication by Sagar et al, which reported activated lipolysis in adipose tissues induced by exosome-transmitted adrenomedullin (AM) from pancreatic cancer (PC) cells.1 Researchers detected AM expressed in PC-derived exosomes and observed elevated AM expression in both tissue and plasma specimens from patients with PC. Biofunctional analysis showed that both AM and PC-derived exosomes promoted lipolysis and this effect could be abolished by blocking the AM receptor, suggesting PC-induced lipolysis is dependent on exosomal AM. A further mechanistic experiment illustrated that the lipolysis induced by AM is mediated through mitogen-activated protein kinases p38 and ERK1/2. Taken together, the results published by Sagar et al reveal a novel molecular mechanism of adipose tissue loss, providing novel insight into early-onset paraneoplastic effects of PC.
Exosomal AM derived from cancer-associated fibroblasts (CAF) promotes lipolysis in adipose tissue. Intriguingly, we noticed that in addition to PC cells, stromal cells also stained positively for AM in …
FK and LL contributed equally.
Contributors XK and ZL conceived and designed the study. FK performed the experiments. LL assisted with study design and wrote the draft. YD and HZ assisted with the acquisition of cancer-associated fibroblast (KPSC) and human adipocyte (HA).
Funding National Natural Science Foundation of China (grant number 81402425).
Competing interests None declared.
Ethics approval Shanghai Changhai Hospital Ethics Committee.
Provenance and peer review Not commissioned; internally peer reviewed.
Correction notice This article has been corrected since it published Online First. The second author’s name has been corrected.
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