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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 …
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