Tumor-environment biomimetics delay peritoneal metastasis formation by deceiving and redirecting disseminated cancer cells

被引：36

作者：

De Vlieghere, Elly ^{[1
]}

Gremonprez, Felix ^{[2
]}

Verset, Laurine ^{[3
]}

Marien, Lore ^{[1
]}

Jones, Christopher J. ^{[4
]}

De Craene, Bram ^{[5
,6
]}

Berx, Geert ^{[5
,6
]}

Descamps, Benedicte ^{[7
]}

Vanhove, Christian ^{[7
]}

Remon, Jean-Paul ^{[8
]}

Ceelen, Wim ^{[2
]}

Demetter, Pieter ^{[3
]}

Bracke, Marc ^{[1
]}

De Geest, Bruno G. ^{[8
]}

De Wever, Olivier ^{[1
]}

机构：

[1] Univ Ghent, Lab Expt Canc Res, B-9000 Ghent, Belgium

[2] Ghent Univ Hosp, Dept Surg, B-9000 Ghent, Belgium

[3] Univ Libre Bruxelles, Erasme Univ Hosp, Dept Pathol, Brussels, Belgium

[4] Univ Wales Coll Cardiff, Coll Med, Dept Pathol, Cardiff CF1 3NS, S Glam, Wales

[5] VIB, Inflammat Res Ctr, Unit Mol & Cellular Oncol, B-9052 Ghent, Belgium

[6] Univ Ghent, Dept Biomed Mol Biol, B-9052 Ghent, Belgium

[7] Univ Ghent, Dept Elect & Informat Syst, IBiTech, MEDISIP,INFINITY, B-9000 Ghent, Belgium

[8] Univ Ghent, Lab Pharmaceut Technol, B-9000 Ghent, Belgium

来源：

BIOMATERIALS | 2015年 / 54卷

关键词：

Cancer-associated fibroblasts; Peritoneal metastasis; Biomimetic trap; Tumor-environment; Cell adhesion; Microencapsulation; CARCINOMA-ASSOCIATED FIBROBLASTS; TENASCIN-C; THERAPY; SURGERY; LAVAGE; AGGREGATION; SURVIVAL; INVASION; RISK;

D O I：

10.1016/j.biomaterials.2015.03.012

中图分类号：

R318 [生物医学工程];

学科分类号：

100103 [病原生物学];

摘要：

Peritoneal metastasis is life threatening and is the result of an extensive communication between disseminated cancer cells, mesothelial cells and cancer-associated fibroblasts (CAF). CAFs secrete extracellular matrix (ECM) proteins creating a receptive environment for peritoneal implantation. Considering cancer as an ecosystem may provide opportunities to exploit CAFs to create biomimetic traps to deceive and redirect cancer cells. We have designed microparticles (MP) containing a CAF-derived ECM-surface that is intended to compete with natural niches. CAFs were encapsulated in alginate/gelatine beads (500-750 mu m in diameter) functionalised with a polyelectrolyte coating (MP[CAF]). The encapsulated CAFs remain viable and metabolically active (>= 35 days), when permanently encapsulated. CAF-derived ECM proteins are retained by the non-biodegradable coating. Adhesion experiments mimicking the environment of the peritoneal cavity show the selective capture of floating cancer cells from different tumor origins by MP[CAF] compared to control MP. MP[CAF] are distributed throughout the abdominal cavity without attachment to intestinal organs and without signs of inflammatory reaction. Intraperitoneal delivery of MP[CAF] and sequential removal redirects cancer cell adhesion from the surgical wound to the MP[CAF], delays peritoneal metastasis formation and prolongs animal survival. Our experiments suggest the use of a biomimetic trap based on tumor environment interactions to delay peritoneal metastasis. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：148 / 157

页数：10

共 46 条

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