Metabolic vulnerability is a target of the antineoplastic effect of breastfeeding

Pappalysin-A (PAPP-A) is an extracellular protease normally expressed on the surface of placental trophoblasts during pregnancy but can also acts as an oncogene. We show that the serum of lactating mice or breastfeeding mothers protects against PAPP-A+ cancers specifically, while serum from virgin mice or parity-matched but non-lactating women do not.

RNAseq revealed that lactating serum targets mitochondrial function in PAPP-A+ cancer cells leading to senescence. Further, we found that overexpression of PAPP-A in cancer cells is associated with lower mitochondrial function. These observations suggest that the anti-tumorigenic effect of lactation serum acts by exploiting the metabolic vulnerability of PAPP-A+ cancer cells.