PDGFRα+ITGA11+ fibroblasts foster early-stage cancer lymphovascular invasion and lymphatic metastasis via ITGA11-SELE interplay
Sun Yat-sen Memorial Hospital · Sun Yat-sen University · +6 more institutions
Abstract
Cancer-associated fibroblasts (CAFs) exhibit considerable heterogeneity in advanced cancers; however, the functional annotation and mechanism of CAFs in early-stage cancers remain elusive. Utilizing single-cell RNA sequencing and spatial transcriptomic, we identify a previously unknown PDGFRα+ITGA11+ CAF subset in early-stage bladder cancer (BCa). Multicenter clinical analysis of a 910-case cohort confirms that PDGFRα+ITGA11+ CAFs are associated with lymphovascular invasion (LVI) and poor prognosis in early-stage BCa. These CAFs facilitate LVI and lymph node (LN) metastasis in early-stage BCa, as evidenced in a PDGFRα+ITGA11+ CAFs-specific deficient mouse model. Mechanistically, PDGFRα+ITGA11+ CAFs promote…
Citation impact
- FWCI
- 31.42
- Percentile
- 100%
- References
- 65
Authors
16- HZHanhao Zheng
Sun Yat-sen Memorial Hospital, Sun Yat-sen University, State Key Laboratory of Oncology in South China
- MAMingjie An
Sun Yat-sen University, Sun Yat-sen Memorial Hospital, State Key Laboratory of Oncology in South China
- YLYuming Luo
Guangdong Academy of Medical Sciences, Guangdong Provincial People's Hospital
- XDXiayao Diao
Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
- WZWenlong Zhong
State Key Laboratory of Oncology in South China, Sun Yat-sen University, Sun Yat-sen Memorial Hospital
Topics & keywords
- Intravasation
- Cancer-Associated Fibroblasts
- Lymphovascular invasion
- Cancer research
- Lymphangiogenesis
- Metastasis
- Biology
- Cancer