Amyloid precursor-like protein 2 expression in macrophages: differentiation and M1/M2 macrophage dynamics
Related Experiment Video
Updated: May 10, 2025
Macrophage Differentiation and Polarization into an M2-Like Phenotype using a Human Monocyte-Like THP-1 Leukemia Cell Line
Published on: August 2, 2021
Gabrielle L Brumfield1,2, Shelby M Knoche1,2, Kenadie R Doty1,2
1Eppley Institute, University of Nebraska Medical Center, Omaha, NE, United States.
Abstract:
Amyloid precursor-like protein 2 (APLP2) has been previously associated with pro-tumor phenotypes in cancer cells, and in this current study we investigated the expression and functions of this protein in macrophages. Our findings showed that APLP2 expression was increased in monocyte-like U937 cells after cytokine-induced differentiation to macrophage-like cells. Evaluation of human mRNA data revealed that APLP2 is more highly expressed in human M2/anti-inflammatory (pro-tumor) macrophages than in M1 macrophages (which have a pro-inflammatory, anti-tumor phenotype). Consistent with the mRNA data, by immunoblotting we identified increased APLP2 protein expression in mouse M2/anti-inflammatory macrophages. Intratumoral infiltration of M2/anti-inflammatory macrophages has been reported in several cancers, including neuroblastoma (NB). We observed that treatment of macrophages with NB-conditioned media induced M2/anti-inflammatory and mixed phenotypes. Through comparison of macrophages from wild-type and APLP2-knockout mice, we correlated alterations in inflammation-associated markers with the presence of APLP2. This suggests that APLP2 influences macrophage polarization dynamics between M0/unpolarized and pro- and anti-inflammatory states, and populations altered by APLP2 KO resemble the macrophage profiles altered with NB-conditioned media treatment. In total, our work implicates APLP2 as a mediator of macrophage status, namely in the M0/unpolarized macrophage and the M1/pro-inflammatory and M2/anti-inflammatory axis.
Insights
Amyloid precursor-like protein 2 (APLP2) drives macrophage polarization towards an anti-inflammatory, pro-tumor M2 state. APLP2 influences macrophage phenotypes, impacting cancer progression and inflammation.
Area of Science:
- Immunology
- Cancer Biology
- Molecular Biology
Background:
- Amyloid precursor-like protein 2 (APLP2) is linked to pro-tumor phenotypes in cancer.
- Macrophages play critical roles in cancer progression and immune response.
- Understanding macrophage polarization is crucial for cancer therapy.
Purpose of the Study:
- To investigate the expression and function of APLP2 in macrophages.
- To determine APLP2's role in macrophage polarization.
- To explore APLP2's involvement in cancer-associated macrophage phenotypes.
Main Methods:
- Cytokine-induced differentiation of U937 cells to macrophages.
- Analysis of human mRNA data for APLP2 expression in M1 vs. M2 macrophages.
- Immunoblotting to detect APLP2 protein in mouse macrophages.
- Treatment of macrophages with neuroblastoma-conditioned media.
- Comparison of macrophages from wild-type and APLP2-knockout mice.
Main Results:
- APLP2 expression increased during macrophage differentiation.
- APLP2 is upregulated in M2 (anti-inflammatory, pro-tumor) macrophages compared to M1 (pro-inflammatory, anti-tumor) macrophages.
- Neuroblastoma-conditioned media induced M2 and mixed macrophage phenotypes.
- APLP2 influences macrophage polarization dynamics between M0, M1, and M2 states.
- APLP2 knockout altered macrophage profiles, mimicking NB-conditioned media effects.
Conclusions:
- APLP2 is a key mediator of macrophage polarization.
- APLP2 promotes an M2 macrophage phenotype, associated with pro-tumorigenic functions.
- APLP2's role in macrophage polarization is relevant to cancer, particularly neuroblastoma.
