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. 2022 Nov 9;54(11):1901–1912. doi: 10.1038/s12276-022-00886-x

Fig. 7. The increase in the HBEGF level induced by particulate matter (PM) contributes to lung cancer metastasis in mice.

Fig. 7

a Hematoxylin and eosin (H&E) staining of lung samples harvested from control and PM-treated mice. Black arrow, immune cells; white arrow, PM. Scale bar, 100 μm. b Quantification of total cells in the bronchoalveolar lavage fluid (BALF) of control and PM-treated mice. c qRT‒PCR analysis of whole lungs from control and PM-treated mice. d qRT‒PCR analysis of macrophages from the lungs of control and PM-treated mice. e Immunoblot analysis of BALF (top line), plasma (middle line), and whole-lung lysate (bottom line) from control and PM-treated mice. β-Actin was used as the loading control for the whole-lung lysate. f In vivo metastasis assay with intravenously injected luciferase-expressing Lewis lung carcinoma (LLC-luc) cells; 24 h after intravenous injection of cells, mice were injected intratracheally three times over 3 days with PM alone or with CRM197 (an inhibitor of HBEGF). IVIS images were acquired 14 days after intravenous injection of cells. g Quantification of bioluminescence (n = 5 mice per group). h Representative images of H&E staining from the in vivo metastasis assay. Scale bar, 500 μm. i Quantification of metastatic lung nodules. j Proposed model of metastasis with PM-exposed macrophages. PM induces HBEGF expression in macrophages through activation of NF-κB and AP-1, which promotes EMT in cancer cells and facilitates metastasis. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001; ns not significant.