Influence of Terminal Differentiation and PACAP on the Cytokine, Chemokine, and Growth Factor Secretion of Mammary Epithelial Cells.

Csanaky, Katalin and Doppler, Wolfgang and Tamás, Andrea and Kovács, Krisztina and Tóth, Gábor and Reglődi, Dóra (2014) Influence of Terminal Differentiation and PACAP on the Cytokine, Chemokine, and Growth Factor Secretion of Mammary Epithelial Cells. Journal of Molecular Neuroscience, 52. pp. 28-36.

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Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide with trophic and cytoprotective effects, has been shown to affect cell survival, proliferation, and also differentiation of various cell types. The high PACAP level in the milk and its changes during lactation suggest a possible effect of PACAP on differentiation of mammary epithelial cells. Mammary cell differentiation is regulated by hormones, growth factors, cytokines/chemokines and angiogenic proteins. In this study, differentiation was hormonally induced by lactogenic hormones in confluent cultures of HC11 mouse mammary epithelial cells. We investigated the effect of PACAP on mammary cell differentiation as well as release of cytokines, chemokines and growth factors. Differentiation was assessed by expression analysis of the milk protein β-casein. Differentiation significantly decreased the secretion of IP-10, RANTES and the EGFR-ligands EGF and amphiregulin. The changes in the levels of IP-10 and RANTES may be relevant for the alterations in homing of T cells and B cells at different stages of mammary gland development, while the changes of the EGFR-ligands may facilitate the switch from proliferative to lactating stage. PACAP did not modulate the expression of β-casein or the activity of hormone induced pathways as determined by analysis of phosphorylation of Akt, STAT5 and p38 MAPK. However, PACAP decreased the release of EGF and amphiregulin from non-differentiated cells. This may influence the extracellular signal related transactivation of EGFR in the non-differentiated mammary epithelium and is considered to have an impact on the modulation of oncogenic EGFR signaling in breast cancer.

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