Multiwalled Carbon Nanotubes-Reprogrammed Macrophages Facilitate Breast Cancer Metastasis via NBR2/TBX1 Axis

• Published in: ACS nano 2024-04, Vol.18 (17), p.11103-11119
• Main Authors: Ding, Keshuo, Zhu, Yaling, Yan, Lang, Zhu, Linyan, Zhang, Tian-Tian, Zhang, Rumeng, Li, Qiushuang, Xie, Bin, Ding, Lin, Shang, Limeng, Wang, Yi, Xu, Panpan, Zhu, Tao, Chen, Chunying, Zhu, Yong
• Format: Article
• Language: English
• Subjects: Animals; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Line, Tumor; Female; Humans; Macrophages - drug effects; Macrophages - metabolism; Mice; Mice, Inbred BALB C; Nanotubes, Carbon - chemistry; Neoplasm Metastasis; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; T-Box Domain Proteins - metabolism
• ISSN: 1936-0851; 1936-086X
• DOI: 10.1021/acsnano.3c11651

In recent years, carbon nanotubes have emerged as a widely used nanomaterial, but their human exposure has become a significant concern. In our former study, we reported that pulmonary exposure of multiwalled carbon nanotubes (MWCNTs) promoted tumor metastasis of breast cancer; macrophages were key effectors of MWCNTs and contributed to the metastasis-promoting procedure in breast cancer, but the underlying molecular mechanisms remain to be explored. As a follow-up study, we herein demonstrated that MWCNT exposure in breast cancer cells and macrophage coculture systems promoted metastasis of breast cancer cells both in vitro and in vivo; macrophages were skewed into M2 polarization by MWCNT exposure. LncRNA NBR2 was screened out to be significantly decreased in MWCNTs-stimulated macrophages through RNA-seq; depletion of NBR2 led to the acquisition of M2 phenotypes in macrophages by activating multiple M2-related pathways. Specifically, NBR2 was found to positively regulate the downstream gene TBX1 through H3k27ac activation. TBX1 silence rescued NBR2-induced impairment of M2 polarization in IL-4 & IL-13-stimulated macrophages. Moreover, NBR2 overexpression mitigated the enhancing effects of MWCNT-exposed macrophages on breast cancer metastasis. This study uncovered the molecular mechanisms underlying breast cancer metastasis induced by MWCNT exposure.