| RRC ID |
85950
|
| Author |
Oo MW, Hikita T, Mashima T, Torigata K, Thu YM, Habu T, Kawai H, Ohara T, Tomida S, Ito S, Suzawa K, Nagatsuka H, Toyooka S, Nakayama M.
|
| Title |
Cancer-associated fibroblast-derived SOD3 enhances lymphangiogenesis to drive metastasis in lung adenocarcinoma.
|
| Journal |
Angiogenesis
|
| Abstract |
Despite advancements in diagnostic and therapeutic strategies, lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality due to its aggressive metastatic potential. Extracellular superoxide dismutase (SOD3) is an antioxidant enzyme that regulates oxidative stress and is regarded as a tumor suppressor. However, studies have demonstrated that SOD3 can either promote or inhibit cell proliferation and survival in various cancers, and its molecular mechanisms within the tumor microenvironment are poorly understood. In this study, we report a breakthrough in uncovering the role of SOD3 derived from cancer-associated fibroblasts (CAFs) in LUAD. Using LUAD xenograft models co-implanted with SOD3-overexpressing CAFs (CAFSOD3), we observe an aggressive tumor phenotype characterized by increased lymphangiogenesis and lymphatic vessel invasion (LVI) of the tumor. Additionally, LUAD patients with elevated SOD3 levels exhibit a higher incidence of LVI and metastasis. Notably, RNA sequencing of CAFSOD3 reveals that SOD3-mediated VEGF-dependent tumor progression and lymphangiogenesis are up-regulated. Furthermore, single-cell transcriptomic analysis of LUAD clinical samples confirms a strong correlation between SOD3 expression in fibroblasts and characteristics of tumor exacerbation, such as lymphangiogenesis and metastasis. These findings underscore new insights into the role of CAF-derived SOD3 in LUAD progression and highlight its potential as a biomarker and therapeutic target.
|
| Volume |
28(4)
|
| Pages |
51
|
| Published |
2025-9-30
|
| DOI |
10.1007/s10456-025-10005-9
|
| PII |
10.1007/s10456-025-10005-9
|
| PMID |
41028519
|
| PMC |
PMC12484251
|
| MeSH |
Adenocarcinoma of Lung* / enzymology
Adenocarcinoma of Lung* / genetics
Adenocarcinoma of Lung* / pathology
Animals
Cancer-Associated Fibroblasts* / enzymology
Cancer-Associated Fibroblasts* / metabolism
Cancer-Associated Fibroblasts* / pathology
Cell Line, Tumor
Female
Humans
Lung Neoplasms* / enzymology
Lung Neoplasms* / genetics
Lung Neoplasms* / pathology
Lymphangiogenesis*
Lymphatic Metastasis
Male
Mice
Neoplasm Metastasis
Neoplasm Proteins* / genetics
Neoplasm Proteins* / metabolism
Superoxide Dismutase* / genetics
Superoxide Dismutase* / metabolism
Tumor Microenvironment
|
| IF |
9.78
|
| Resource |
| Human and Animal Cells |
PC-9(RCB4455) |
