Abstract
There is increasing evidence that the complement system is activated in various cancer tissues. Besides being involved in innate immunity against pathogens, the complement system also participates in inflammation and the modulation of tumor microenvironment. Recent studies suggest that complement activation promotes tumor progression in various ways. Among some cancer cell lines, we found that human bone osteosarcoma epithelial cells (U2-OS) can activate the alternative pathway of the complement system by pooled normal human serum. Interestingly, U2-OS cells showed less expression of complement regulatory proteins, compared to other cancer cell lines. Furthermore, the activated complement system enhanced the production of growth factors, which promoted angiogenesis of human endothelial cells. Our results demonstrated a direct linkage between the complement system and angiogenesis using the in vitro model, which suggest the complement system and related mechanisms might be potential targets for cancer treatment.
Highlights
The complement system is an effector of innate immunity and a participant in the adaptive immune response, inflammation, hemostasis, and more[1]
To confirm if U2-OS cells can activate the complement system, the deposition of membrane attack complex (MAC) and C3b on cells were analyzed by an immunofluorescence assay (IFA) and flow cytometry, respectively (Fig. 1B,C)
Few apoptosis and cell death was observed both in normal human serum (NHS)- and heat-inactivated human serum (HHS)-treated cells (Fig. 1E), suggesting that the activated complement system does not induce cell death in U2-OS cells. These results indicate that U2-OS cells have a potential to be used for complement activation with sublytic level of MAC
Summary
The complement system is an effector of innate immunity and a participant in the adaptive immune response, inflammation, hemostasis, and more[1]. The formation of a membrane attack complex (MAC) in complement activation leads to structural pores within cell membranes, resulting in cell death by osmotic fluid shifts and cation influx[6]; many nucleated eukaryotic cells have defensive mechanisms against MAC-mediated destruction. This so-called sublytic MAC induces different effects on cells, including activation of the cell cycle, growth factor release, and protection from apoptotic cell death, among others[7,8,9,10]. We demonstrate for the first time activation of the complement system in osteosarcoma cells using NHS, and the complement system’s impact on angiogenesis
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