Affiliation:
1. Department of Oral and Maxillofacial Surgery The Second Xiangya Hospital of Central South University Changsha Hunan 410011 China
2. NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine Central South University Changsha Hunan 410078 China
3. Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education Cancer Research Institute and School of Basic Medicine Sciences Central South University Changsha Hunan 410078 China
4. Department of Stomatology Xiangya Hospital Central South University Changsha Hunan 410008 China
Abstract
AbstractIn South and Southeast Asia, the habit of chewing betel nuts is prevalent, which leads to oral submucous fibrosis (OSF). OSF is a well‐established precancerous lesion, and a portion of OSF cases eventually progress to oral squamous cell carcinoma (OSCC). However, the specific molecular mechanisms underlying the malignant transformation of OSCC from OSF are poorly understood. In this study, the leading‐edge techniques of Spatial Transcriptomics (ST) and Spatial Metabolomics (SM) are integrated to obtain spatial location information of cancer cells, fibroblasts, and immune cells, as well as the transcriptomic and metabolomic landscapes in OSF‐derived OSCC tissues. This work reveals for the first time that some OSF‐derived OSCC cells undergo partial epithelial–mesenchymal transition (pEMT) within the in situ carcinoma (ISC) region, eventually acquiring fibroblast‐like phenotypes and participating in collagen deposition. Complex interactions among epithelial cells, fibroblasts, and immune cells in the tumor microenvironment are demonstrated. Most importantly, significant metabolic reprogramming in OSF‐derived OSCC, including abnormal polyamine metabolism, potentially playing a pivotal role in promoting tumorigenesis and immune evasion is discovered. The ST and SM data in this study shed new light on deciphering the mechanisms of OSF‐derived OSCC. The work also offers invaluable clues for the prevention and treatment of OSCC.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Hunan Province
Subject
General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)