CTC-derived pancreatic cancer models serve as research tools and are suitable for precision medicine approaches

被引:1
作者
Tang, Jiajia [1 ,2 ]
Zheng, Quan [1 ,2 ]
Wang, Qi [1 ,2 ]
Zhao, Yaru [1 ,2 ]
Ananthanarayanan, Preeta [3 ]
Reina, Chiara [3 ]
Sabanovic, Berina [3 ]
Jiang, Ke [1 ,2 ]
Yang, Ming-Hsin [4 ]
Meny, Clara Csilla [5 ]
Wang, Huimin [1 ,2 ]
Agerbaek, Mette O. [6 ,7 ]
Clausen, Thomas Mandel [6 ]
Gustavsson, Tobias [6 ,8 ]
Wen, Chenlei [9 ,10 ,11 ]
Borghi, Felice [12 ]
Mellano, Alfredo [12 ]
Fenocchio, Elisabetta [13 ]
Gregorc, Vanesa [13 ]
Sapino, Anna [14 ]
Theander, Thor G. [6 ]
Fu, Da [9 ,10 ,11 ]
Aicher, Alexandra [15 ,16 ]
Salanti, Ali [6 ]
Shen, Baiyong [9 ,10 ,11 ]
Heeschen, Christopher [1 ,2 ,3 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Publ Hlth, Sch Med, Ctr Single Cell Om, Shanghai 200025, Peoples R China
[2] Shanghai Jiao Tong Univ, Sch Med, State Key Lab Syst Med Canc, Shanghai 200025, Peoples R China
[3] Candiolo Canc Inst FPO IRCCS, Pancreat Canc Heterogene, I-10060 Candiolo, Turin, Italy
[4] Triserv Gen Hosp, Natl Def Med Ctr, Dept Surg, Div Urol, Taipei 114, Taiwan
[5] Semmelweis Univ, Inst Pathol & Expt Oncol Res 2, H-1085 Budapest, Hungary
[6] Univ Copenhagen, Ctr Translat Med & Parasitol CMP, Dept Immunol & Microbiol, DK-2200 Copenhagen, Denmark
[7] VarCT Diagnost, Ole Maaloes Vej 3, DK-2200 Copenhagen, Denmark
[8] VAR2pharmaceuticals, Ole Maaloes Vej 3, DK-2200 Copenhagen, Denmark
[9] Shanghai Jiao Tong Univ, Ruijin Hosp, Sch Med, Res Inst Pancreat Dis, Shanghai, Peoples R China
[10] Shanghai Jiao Tong Univ, Ruijin Hosp, Pancreat Dis Ctr, Sch Med, Shanghai, Peoples R China
[11] Shanghai Jiao Tong Univ, Ruijin Hosp, Shanghai Inst Digest Surg, Sch Med, Shanghai, Peoples R China
[12] Canc Inst FPO IRCCS, Dept Surg Oncol, I-10060 Candiolo, Turin, Italy
[13] Canc Inst FPO IRCCS, Dept Med Oncol, I-10060 Candiolo, Turin, Italy
[14] Canc Inst FPO IRCCS, Dept Pathol, I-10060 Candiolo, Turin, Italy
[15] China Med Univ, Grad Inst Biomed Sci, Precis Immunotherapy, Taichung, Taiwan
[16] China Med Univ, Immunol Res & Dev Ctr, Taichung, Taiwan
关键词
CIRCULATING TUMOR-CELLS; STEM-CELLS; EPITHELIAL-CELLS; BREAST-CANCER; BONE-MARROW; ADENOCARCINOMA; TUMORIGENICITY; INHIBITION; EXPRESSION;
D O I
10.1016/j.xcrm.2024.101692
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
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页数:27
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