Identification and Characterization of Cancer-Associated Fibroblast Subpopulations in Lung Adenocarcinoma
- 주제(키워드) cancer-associated fibroblasts , single-cell RNA sequencing , lung adenocarcinoma , tumor microenvironment , heterogeneity
- 주제(기타) Oncology
- 설명문(일반) [Kim, Daeseung] Deargen Inc, Daejeon 34051, South Korea; [Kim, Jeong Seon; Cheon, Inyoung; Lee, Sieun; Ahn, Young-Ho] Ewha Womans Univ, Coll Med, Dept Mol Med, Seoul 07804, South Korea; [Kim, Jeong Seon; Cheon, Inyoung; Lee, Sieun; Ahn, Young-Ho] Ewha Womans Univ, Coll Med, Inflammat Canc Microenvironm Res Ctr, Seoul 07804, South Korea; [Kim, Jeong Seon] Univ Kentucky, Dept Mol & Cellular Biochem, Lexington, KY 40536 USA; [Kim, Seo Ree; Chun, Sang Hoon; Won, Hye Sung; Ko, Yoon Ho] Catholic Univ Korea, Coll Med, Dept Internal Med, Div Oncol, Seoul 06591, South Korea; [Kim, Jae Jun] Catholic Univ Korea, Uijeongbu St Marys Hosp, Coll Med, Dept Thorac & Cardiovasc Surg, Seoul 06591, South Korea; [Yoon, Jung Sook] Catholic Univ Korea, Uijeongbu St Marys Hosp, Clin Res Lab, Uijongbu 11765, South Korea; [Hong, Soon Auck] Chung Ang Univ, Coll Med, Dept Pathol, Seoul 06974, South Korea; [Kang, Keunsoo] Dankook Univ, Coll Sci & Technol, Dept Microbiol, Cheonan 31116, South Korea; [Ko, Yoon Ho] Catholic Univ Korea, Coll Med, Canc Res Inst, Seoul 06591, South Korea
- 등재 SCIE, SCOPUS
- OA유형 Green Published, gold
- 발행기관 MDPI
- 발행년도 2022
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000194609
- 본문언어 영어
- Published As https://doi.org/10.3390/cancers14143486
- PubMed https://pubmed.ncbi.nlm.nih.gov/35884546
초록/요약
Simple Summary Considering that cancer-associated fibroblasts (CAFs) facilitate cancer cell motility, invasiveness, and drug resistance, heterogeneity within the CAF population may be of major significance during cancer progression and metastasis. Through pseudotime trajectory analysis of single-cell RNA sequencing data, we revealed several subpopulations of lung CAFs with distinct gene expression patterns, namely, immunosuppressive, neoantigen-presenting, myofibroblastic, and proliferative CAFs. The knockdown of KPNA2, one of the neoantigen-presenting CAF-specific markers, attenuated CAF invasiveness, suggesting that CAF subtype markers may represent therapeutic targets within the tumor microenvironment of lung cancer patients. Cancer-associated fibroblasts (CAFs) reside within the tumor microenvironment, facilitating cancer progression and metastasis via direct and indirect interactions with cancer cells and other stromal cell types. CAFs are composed of heterogeneous subpopulations of activated fibroblasts, including myofibroblastic, inflammatory, and immunosuppressive CAFs. In this study, we sought to identify subpopulations of CAFs isolated from human lung adenocarcinomas and describe their transcriptomic and functional characteristics through single-cell RNA sequencing (scRNA-seq) and subsequent bioinformatics analyses. Cell trajectory analysis of combined total and THY1 + CAFs revealed two branching points with five distinct branches. Based on Gene Ontology analysis, we denoted Branch 1 as "immunosuppressive", Branch 2 as "neoantigen presenting", Branch 4 as "myofibroblastic", and Branch 5 as "proliferative" CAFs. We selected representative branch-specific markers and measured their expression levels in total and THY1 + CAFs. We also investigated the effects of these markers on CAF activity under coculture with lung cancer cells. This study describes novel subpopulations of CAFs in lung adenocarcinoma, highlighting their potential value as therapeutic targets.
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