How air pollution alters lung tissue, increasing cancer susceptibility
Date:
April 19, 2022
Source:
eLife
Summary:
Scientists have identified a mechanism that explains how fine
air pollution particles might cause lung cancer, according to a
new study.
FULL STORY ========================================================================== Scientists have identified a mechanism that explains how fine air
pollution particles might cause lung cancer, according to a study
published today in eLife.
==========================================================================
The findings could lead to new approaches for preventing or treating
the initial lung changes that lead to the disease.
Tiny, inhalable fine particulate matter (FPM) found in air pollutants
has been recognised as a Group 1 carcinogen and a substantial threat to
global health.
However, the cancer-causing mechanism of FPM remains unclear.
"Despite its potential to cause mutations, recent research suggests that
FPM does not directly promote -- and may even inhibit -- the growth of
lung cancer cells," explains first author Zhenzhen Wang, an associate researcher at Nanjing University (NJU), Nanjing, China, who carried
out the study between labs at NJU and the University of Macau where she
was sponsored by a University of Macau Fellowship. "This suggests that
FPM might lead to cancer through indirect means that support tumour
growth. For example, some studies suggest FPM can prevent immune cells
from moving to where they are needed." To explore this possibility, Wang
and the team collected FPM from seven locations in China and studied its effects on the main immune cells that defend against tumour growth --
called cytotoxic T-cells (CTLs). In mice administered with lung cancer
cells that were not exposed to FPM, CTLs were recruited to the lung to
destroy the tumour cells. By contrast, in the mice whose lungs were
exposed to FPM, the infiltration of CTLs was delayed -- potentially
allowing the tumour cells to establish in lung tissue.
To investigate why the CTLs did not enter the lung as quickly in the
FPM- exposed lungs, the team studied both the CTLs themselves and
the lung tissue structure. They found that CTLs exposed to FPM still
retained their migratory ability, but that FPM exposure dramatically
compressed the lung tissue structure and the spaces that immune cells
move between. There were also much higher levels of collagen -- a protein
that provides biomechanical support for cells and tissues. When the team studied the movement of CTLs in the mice, in lung tissue exposed to FPM,
CTLs struggled to move, whereas those in the untreated tissue were able
to move freely.
Further analysis of the tissue showed that the structural changes were
caused by increases in a collagen subtype called collagen IV, but the
team still did not know how FPM triggered this. They found the answer
when they looked more closely at the structural changes to collagen IV
and the enzyme responsible for making them -- called peroxidasin. This
enzyme drives a specific type of cross- linking that exposure to FPM
was found to cause and aggravate in the lung tissue.
"The most surprising find was the mechanism by which this process
occurred," Wang says. "The peroxidasin enzyme stuck to the FPM in
the lung, which increased its activity. Taken together, this means
that wherever FPM lands in the lung, increased peroxidasin activity
leads to structural changes in the lung tissue that can keep immune
cells out and away from growing tumour cells." "Our study reveals a
completely new mechanism by which inhaled fine particles promote lung
tumour development," concludes senior author Lei Dong, Professor at
the School of Life Sciences, Nanjing University. "We provide direct
evidence that proteins that stick to fine particulate matter can cause a significant and adverse effect, giving rise to pathogenic activity. Our discovery that peroxidasin is the mediator of this effect in lung tissue identifies it as a specific and unexpected target for preventing lung
disease caused by air pollution."
========================================================================== Story Source: Materials provided by eLife. Note: Content may be edited
for style and length.
========================================================================== Journal Reference:
1. Zhenzhen Wang, Ziyu Zhai, Chunyu Chen, Xuejiao Tian, Zhen Xing,
Panfei
Xing, Yushun Yang, Junfeng Zhang, Chunming Wang, Lei Dong. Air
pollution particles hijack peroxidasin to disrupt immunosurveillance
and promote lung cancer. eLife, 2022; 11 DOI: 10.7554/eLife.75345 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/04/220419112520.htm
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