Xin Huang1, Chaobin He1, Guohe Lin2, Lianghe Lu3, Kaili Xing1, Xin Hua4, Shuxin Sun1, Yize Mao1, Yunda Song1, Jun Wang1, Shengping Li5. 1. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China; Department of Pancreatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China. 2. Department of Oncology, The Second Affiliated Hospital of AnHui Medical University, Hefei, China. 3. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China; Department of Hepatic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China. 4. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China; Department of Breast Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China. 5. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China; Department of Pancreatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China. Electronic address: lishp@sysucc.org.cn.
Abstract
OBJECTIVE: Tumor associated macrophages (TAMs) promoted pancreatic ductal adenocarcinoma (PDAC) initiation and progression. In this study we aimed to evaluate CD10 expression by monocytes/macrophages and its clinical significance in PDAC. METHODS: Human CD14+ peripheral blood monocytes were isolated and cultured for 6-7 days to differentiate into macrophages in vitro. Monocytic THP-1 cells were cultured and treated with 100 ng/ml phorbol 12-myristate 13-acetate (PMA) for 72 h to induce macrophage differentiation. Reverse transcription-quantitative PCR, immunohistochemistry, immunofluorescence, multiplex immunohistochemical staining and flow cytometry were performed to detect CD10 expression. In addition, the correlations between CD10 expression and immune cells infiltration were investigated through TIMER or GEPIA. Finally, Kaplan-Meier plotter and GEPIA databases were adopted to evaluate the influence of CD10 on clinical prognosis. RESULTS: Our results indicated that CD10 was expressed by a subset of human monocytes and many more cells expressed CD10 after differentiation into macrophages in vitro (13.19% vs. 41.39%; P < 0.0001). As for PDAC tissues, CD10 was correlated with immune cells infiltration and was expressed by a subset of TAMs. For THP-1 cells, PMA could induce CD10 expression through the MAPK pathway. The Kaplan-Meier plotter results suggested that CD10 expression had an impact on the prognosis of PDAC. CONCLUSIONS: In this study we demonstrated that CD10 was expressed by human primary monocytes, human monocyte-derived macrophages and TAMs, and was correlated with poor prognosis in PDAC, suggesting CD10 to be a potential therapeutic target in PDAC.
OBJECTIVE: Tumor associated macrophages (TAMs) promoted pancreatic ductal adenocarcinoma (PDAC) initiation and progression. In this study we aimed to evaluate CD10 expression by monocytes/macrophages and its clinical significance in PDAC. METHODS:HumanCD14+ peripheral blood monocytes were isolated and cultured for 6-7 days to differentiate into macrophages in vitro. Monocytic THP-1 cells were cultured and treated with 100 ng/ml phorbol 12-myristate 13-acetate (PMA) for 72 h to induce macrophage differentiation. Reverse transcription-quantitative PCR, immunohistochemistry, immunofluorescence, multiplex immunohistochemical staining and flow cytometry were performed to detect CD10 expression. In addition, the correlations between CD10 expression and immune cells infiltration were investigated through TIMER or GEPIA. Finally, Kaplan-Meier plotter and GEPIA databases were adopted to evaluate the influence of CD10 on clinical prognosis. RESULTS: Our results indicated that CD10 was expressed by a subset of human monocytes and many more cells expressed CD10 after differentiation into macrophages in vitro (13.19% vs. 41.39%; P < 0.0001). As for PDAC tissues, CD10 was correlated with immune cells infiltration and was expressed by a subset of TAMs. For THP-1 cells, PMA could induce CD10 expression through the MAPK pathway. The Kaplan-Meier plotter results suggested that CD10 expression had an impact on the prognosis of PDAC. CONCLUSIONS: In this study we demonstrated that CD10 was expressed by human primary monocytes, human monocyte-derived macrophages and TAMs, and was correlated with poor prognosis in PDAC, suggesting CD10 to be a potential therapeutic target in PDAC.
Authors: Jonas Schulte-Schrepping; Nico Reusch; Daniela Paclik; Kevin Baßler; Stephan Schlickeiser; Bowen Zhang; Benjamin Krämer; Tobias Krammer; Sophia Brumhard; Lorenzo Bonaguro; Elena De Domenico; Daniel Wendisch; Martin Grasshoff; Theodore S Kapellos; Michael Beckstette; Tal Pecht; Adem Saglam; Oliver Dietrich; Henrik E Mei; Axel R Schulz; Claudia Conrad; Désirée Kunkel; Ehsan Vafadarnejad; Cheng-Jian Xu; Arik Horne; Miriam Herbert; Anna Drews; Charlotte Thibeault; Moritz Pfeiffer; Stefan Hippenstiel; Andreas Hocke; Holger Müller-Redetzky; Katrin-Moira Heim; Felix Machleidt; Alexander Uhrig; Laure Bosquillon de Jarcy; Linda Jürgens; Miriam Stegemann; Christoph R Glösenkamp; Hans-Dieter Volk; Christine Goffinet; Markus Landthaler; Emanuel Wyler; Philipp Georg; Maria Schneider; Chantip Dang-Heine; Nick Neuwinger; Kai Kappert; Rudolf Tauber; Victor Corman; Jan Raabe; Kim Melanie Kaiser; Michael To Vinh; Gereon Rieke; Christian Meisel; Thomas Ulas; Matthias Becker; Robert Geffers; Martin Witzenrath; Christian Drosten; Norbert Suttorp; Christof von Kalle; Florian Kurth; Kristian Händler; Joachim L Schultze; Anna C Aschenbrenner; Yang Li; Jacob Nattermann; Birgit Sawitzki; Antoine-Emmanuel Saliba; Leif Erik Sander Journal: Cell Date: 2020-08-05 Impact factor: 41.582