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Published on: November 28, 2019
Modulating tumor-associated macrophage polarization by anti-maRCO mAb exerts anti-osteosarcoma effects through
Lei Ding1, Ling Wu2, Yuting Cao3
1Department of Orthopedic Surgery, Fudan University Jinshan Hospital, Shanghai, China.
Purpose:
Osteosarcoma is a primary bone tumor lacking optimal clinical treatment options. Tumor-associated macrophages in the tumor microenvironment are closely associated with tumor development and metastasis. Studies have identified the macrophage receptor with collagenous structure (MARCO) as a specific receptor expressed in macrophages. This study aimed to investigate whether anti-MARCO mAb treatment can induce macrophage polarization in the tumor microenvironment and elicit anti-tumor effects.
Methods:
THP-1 cells were treated with 20 ng/mL phorbol 12-myristate 13-acetate and 80 ng/mL interleukin-4 for 48 h to induce macrophage polarization to alternatively activated macrophages (M2). Enzyme-linked immunosorbent assay, real-time quantitative polymerase chain reaction, flow cytometry, and bioinformatic analyses were performed to evaluate macrophage polarization. The co-culture groups included a blank group, an M2 macrophage and U2OS co-culture group, and an anti-MARCO mAb-treated M2 macrophage group. Cell viability assays, cell scratch tests, apoptosis, and cell cycle analyses were performed to determine the effects of anti-MARCO mAb-treated macrophages on osteosarcoma cells.
Results:
It was demonstrated that anti-MARCO mAb can drive macrophages toward classically activated macrophage (M1) polarization. Anti-MARCO mAb promoted the secretion of pro-inflammatory factors by macrophages, including tumor necrosis factor-alpha (TNF-α), interleukin-1beta, interleukin-6 and interleukin-23. Studies on in vitro co-culture models have revealed that macrophages treated with anti-MARCO mAb can suppress the growth and migration of osteosarcoma cells, induce cell apoptosis, and inhibit cell cycle progression of osteosarcoma cells through M1 polarization of macrophages in vitro.
Conclusion:
Anti-MARCO mAb treatment exerts anti-osteosarcoma effects by affecting macrophage polarization toward M1 macrophages, offering a potential new therapeutic approach for treating osteosarcoma.
Insights
Anti-MARCO mAb treatment shifts tumor-associated macrophages to M1, suppressing osteosarcoma growth and metastasis. This offers a novel therapeutic strategy for osteosarcoma by targeting macrophage polarization.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Osteosarcoma, a primary bone tumor, has limited treatment options.
- Tumor-associated macrophages (TAMs) within the tumor microenvironment influence osteosarcoma progression and metastasis.
- Macrophage receptor with collagenous structure (MARCO) is a specific macrophage receptor implicated in tumor biology.
Purpose of the Study:
- To investigate the potential of anti-MARCO mAb treatment to induce macrophage polarization.
- To evaluate the anti-tumor effects of anti-MARCO mAb-modulated macrophages in osteosarcoma.
Main Methods:
- THP-1 cells were differentiated into M2 macrophages.
- Macrophage polarization was assessed using ELISA, qPCR, and flow cytometry.
- In vitro co-culture models with osteosarcoma cells (U2OS) were used to evaluate the effects of anti-MARCO mAb-treated macrophages on tumor cell viability, migration, apoptosis, and cell cycle.
Main Results:
- Anti-MARCO mAb treatment induced a shift in macrophages towards classically activated (M1) polarization.
- Macrophages treated with anti-MARCO mAb secreted pro-inflammatory cytokines, including TNF-α, IL-1β, IL-6, and IL-23.
- In vitro, anti-MARCO mAb-treated macrophages suppressed osteosarcoma cell growth and migration, induced apoptosis, and inhibited cell cycle progression.
Conclusions:
- Anti-MARCO mAb treatment demonstrates anti-osteosarcoma efficacy by promoting M1 macrophage polarization.
- This approach represents a potential new therapeutic strategy for osteosarcoma by modulating the tumor microenvironment.
