Elucidating novel function(s) of prolactin inducible protein in regulating natural killer (NK) cell biology

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Date
2025-02-19
Authors
Okeke, Obinna Innocent
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Abstract

Prolactin-inducible protein (PIP) is found in various bodily fluids, including tears, saliva, sweat, amniotic fluid, and seminal plasma. This protein is frequently associated with breast cancers (BCs) and serves as a biomarker for identifying the origin of BC. Its presence has been linked to favorable prognostic outcomes in human BC. In a 4T1 breast cancer mouse model, ectopic expression of PIP led to an increased frequency of natural killer (NK) cells and dendritic cells within the tumor microenvironment, resulting in delayed tumor onset and reduced growth. While previous research has associated PIP with immune response regulation, the specific mechanisms by which PIP modulates NK cell biology remain unclear. I hypothesized that PIP acts as a novel host factor influencing NK cell functionality. To investigate this, I examined its role in regulating NK cell migration, cytotoxicity, and cytokine production. To assess PIP’s impact on NK cell migration, a transwell migration assay was conducted. NK cells showed significantly enhanced migration toward conditioned media from PIP-expressing 4T1 cells compared to empty vector (EV) controls. Additionally, recombinant mouse PIP (mPIP) at a concentration of 1µg/600ul significantly induced NK cell migration compared to BSA. Treatment of NK cells with PIP also resulted in significant phosphorylation of p38 MAPK and IκBα, suggesting a potential mechanism for PIP’s regulation of NK cell migration. However, the expression of PIP did not affect NK cell-mediated killing or interferon-gamma (IFN-γ) production in response to parental, breast-derived, and lung-metastatic 4T1 cells in vitro. In summary, these findings demonstrate that PIP promotes NK cell migration but does not directly influence NK cell-mediated cytotoxicity or cytokine production in vitro. This study provides novel insights into PIP’s role in enhancing NK cell migration, contributing to a better understanding of its involvement in immune regulation.

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NK migration, 4T1 breast tumor cells, NK cytotoxicity
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