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bioRxiv · 10.1101/2021.12.17.473156

Air Pollution Particles Hijack Peroxidasin to Disrupt Immunosurveillance and Promote Lung Cancer

Wang, Z.·Zhai, Z.·Chen, C.·Tian, X.·Xing, Z.·Xing, P.·Yang, Y.·Zhang, J.·Wang, C.·Dong, L.
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Abstract

Although fine particulate matter (FPM) in air pollutants and tobacco smoke is recognized as a strong carcinogen and global threat to public health, its biological mechanism for inducing lung cancer remains unclear. Here, by investigating FPMs bioactivities in lung carcinoma mice models, we discover that these particles promote lung tumor progression by inducing aberrant thickening of tissue matrix and hampering migration of anti-tumor immunocytes. Upon inhalation into lung tissue, these FPM particles abundantly adsorb peroxidasin (PXDN) - an enzyme mediating type IV collagen (Col IV) crosslinking - onto their surface. The adsorbed PXDN exerts abnormally high activity to crosslink Col IV via increasing the formation of sulfilimine bonds at the NC1 domain, leading to an overly dense matrix in the lung tissue. This disordered structure decreases the mobility of cytotoxic CD8+ T lymphocytes into the lung and consequently impairs the local immune surveillance, enabling the flourish of nascent tumor cells. Meanwhile, inhibiting the activity of PXDN effectively abolishes the tumor-promoting effect of FPM, indicating the key impact of aberrant PXDN activity on tumorigenic process. In summary, our finding elucidates a new mechanism for FPM-induced lung tumorigenesis and identifies PXDN as a potential target for treatment or prevention of the FPM-relevant biological risks. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=181 HEIGHT=200 SRC="FIGDIR/small/473156v1_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@12b72b2org.highwire.dtl.DTLVardef@1770adforg.highwire.dtl.DTLVardef@6ac69corg.highwire.dtl.DTLVardef@154cce_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Wang, Z., Zhai, Z., Chen, C., Tian, X., Xing, Z., Xing, P., Yang, Y., Zhang, J., Wang, C., Dong, L.. 2021-12-20. Air Pollution Particles Hijack Peroxidasin to Disrupt Immunosurveillance and Promote Lung Cancer. https://doi.org/10.1101/2021.12.17.473156

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