Prolactin is best known as the
polypeptide anterior pituitary
hormone, which regulates the development of the mammary gland. However, it became clear over the last decade that
prolactin contributes to a broad range of pathologies, including
breast cancer.
Prolactin is also involved in angiogenesis via the release of pro-angiogenic factors by leukocytes and epithelial cells. However, whether
prolactin also influences endothelial cells, and whether there are functional consequences of
prolactin-induced signalling in the perspective of angiogenesis, remains so far elusive. In the present study, we show that
prolactin induces phosphorylation of ERK1/2 and STAT5 and induces tube formation of endothelial cells on
Matrigel. These effects are blocked by a specific
prolactin receptor antagonist, del1-9-G129R-hPRL. Moreover, in an in vivo model of the chorioallantoic membrane of the chicken embryo,
prolactin enhances vessel density and the tortuosity of the vasculature and pillar formation, which are hallmarks of intussusceptive angiogenesis. Interestingly, while
prolactin has only little effect on endothelial cell proliferation, it markedly stimulates endothelial cell migration. Again, migration was reverted by del1-9-G129R-hPRL, indicating a direct effect of
prolactin on its receptor. Immunohistochemistry and spectral imaging revealed that the
prolactin receptor is present in the microvasculature of human
breast carcinoma tissue. Altogether, these results suggest that
prolactin may directly stimulate angiogenesis, which could be one of the mechanisms by which
prolactin contributes to
breast cancer progression, thereby providing a potential tool for intervention.