Cell Reports Medicine (Sep 2024)
CTC-derived pancreatic cancer models serve as research tools and are suitable for precision medicine approaches
- Jiajia Tang,
- Quan Zheng,
- Qi Wang,
- Yaru Zhao,
- Preeta Ananthanarayanan,
- Chiara Reina,
- Berina Šabanović,
- Ke Jiang,
- Ming-Hsin Yang,
- Clara Csilla Meny,
- Huimin Wang,
- Mette Ø. Agerbaek,
- Thomas Mandel Clausen,
- Tobias Gustavsson,
- Chenlei Wen,
- Felice Borghi,
- Alfredo Mellano,
- Elisabetta Fenocchio,
- Vanesa Gregorc,
- Anna Sapino,
- Thor G. Theander,
- Da Fu,
- Alexandra Aicher,
- Ali Salanti,
- Baiyong Shen,
- Christopher Heeschen
Affiliations
- Jiajia Tang
- Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; State Key Laboratory of Systems Medicine for Cancer, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Quan Zheng
- Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; State Key Laboratory of Systems Medicine for Cancer, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Qi Wang
- Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; State Key Laboratory of Systems Medicine for Cancer, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Yaru Zhao
- Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; State Key Laboratory of Systems Medicine for Cancer, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Preeta Ananthanarayanan
- Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute FPO-IRCCS, 10060 Candiolo, Turin, Italy
- Chiara Reina
- Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute FPO-IRCCS, 10060 Candiolo, Turin, Italy
- Berina Šabanović
- Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute FPO-IRCCS, 10060 Candiolo, Turin, Italy
- Ke Jiang
- Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; State Key Laboratory of Systems Medicine for Cancer, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Ming-Hsin Yang
- Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan
- Clara Csilla Meny
- 2nd Institute for Pathology and Experimental Oncology Research, Semmelweis University, 1085 Budapest, Hungary
- Huimin Wang
- Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; State Key Laboratory of Systems Medicine for Cancer, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Mette Ø. Agerbaek
- Centre for Translational Medicine and Parasitology (CMP) at Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen N, Denmark; VarCT Diagnostics, Ole Maaloes vej 3, 2200 Copenhagen, Denmark
- Thomas Mandel Clausen
- Centre for Translational Medicine and Parasitology (CMP) at Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen N, Denmark
- Tobias Gustavsson
- Centre for Translational Medicine and Parasitology (CMP) at Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen N, Denmark; VAR2Pharmaceuticals, Ole Maaloes vej 3, 2200 Copenhagen, Denmark
- Chenlei Wen
- Research Institute of Pancreatic Disease, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Pancreatic Disease Centre, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Felice Borghi
- Department of Surgical Oncology, Cancer Institute FPO-IRCCS, 10060 Candiolo, Turin, Italy
- Alfredo Mellano
- Department of Surgical Oncology, Cancer Institute FPO-IRCCS, 10060 Candiolo, Turin, Italy
- Elisabetta Fenocchio
- Department of Medical Oncology, Cancer Institute FPO-IRCCS, 10060 Candiolo, Turin, Italy
- Vanesa Gregorc
- Department of Medical Oncology, Cancer Institute FPO-IRCCS, 10060 Candiolo, Turin, Italy
- Anna Sapino
- Department of Pathology, Cancer Institute FPO-IRCCS, 10060 Candiolo, Turin, Italy
- Thor G. Theander
- Centre for Translational Medicine and Parasitology (CMP) at Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen N, Denmark
- Da Fu
- Research Institute of Pancreatic Disease, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Pancreatic Disease Centre, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Alexandra Aicher
- Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404328, Taiwan; Immunology Research and Development Center, China Medical University, Taichung 404328, Taiwan
- Ali Salanti
- Centre for Translational Medicine and Parasitology (CMP) at Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen N, Denmark
- Baiyong Shen
- Research Institute of Pancreatic Disease, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Pancreatic Disease Centre, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Corresponding author
- Christopher Heeschen
- Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; State Key Laboratory of Systems Medicine for Cancer, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute FPO-IRCCS, 10060 Candiolo, Turin, Italy; Corresponding author
- Journal volume & issue
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Vol. 5,
no. 9
p. 101692
Abstract
Summary: Pancreatic ductal adenocarcinoma (PDAC) poses significant clinical challenges, often presenting as unresectable with limited biopsy options. Here, we show that circulating tumor cells (CTCs) offer a promising alternative, serving as a “liquid biopsy” that enables the generation of in vitro 3D models and highly aggressive in vivo models for functional and molecular studies in advanced PDAC. Within the retrieved CTC pool (median 65 CTCs/5 mL), we identify a subset (median content 8.9%) of CXCR4+ CTCs displaying heightened stemness and metabolic traits, reminiscent of circulating cancer stem cells. Through comprehensive analysis, we elucidate the importance of CTC-derived models for identifying potential targets and guiding treatment strategies. Screening of stemness-targeting compounds identified stearoyl-coenzyme A desaturase (SCD1) as a promising target for advanced PDAC. These results underscore the pivotal role of CTC-derived models in uncovering therapeutic avenues and ultimately advancing personalized care in PDAC.
