title: Tumor-environment biomimetics delay peritoneal metastasis formation by deceiving and redirecting disseminated cancer cells.
abstract: 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 μm 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.
authors.affiliation: Laboratory of Experimental Cancer Research, Ghent University, Belgium.
authors.forename: Elly
authors.initials: E
authors.lastname: De Vlieghere
authors.affiliation: Department of Surgery, Ghent University Hospital, Belgium.
authors.forename: Félix
authors.initials: F
authors.lastname: Gremonprez
authors.affiliation: Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles, Belgium.
authors.forename: Laurine
authors.initials: L
authors.lastname: Verset
authors.affiliation: Laboratory of Experimental Cancer Research, Ghent University, Belgium.
authors.forename: Lore
authors.initials: L
authors.lastname: Mariën
authors.affiliation: Department of Pathology, University of Wales College of Medicine, UK.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Jones
authors.affiliation: Unit of Molecular and Cellular Oncology, Inflammation Research Center, VIB, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium.
authors.forename: Bram
authors.initials: B
authors.lastname: De Craene
authors.affiliation: Unit of Molecular and Cellular Oncology, Inflammation Research Center, VIB, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Berx
authors.affiliation: Department of Electronics and Information Systems, IBiTech, MEDISIP, INFINITY, Ghent University, Belgium.
authors.forename: Benedicte
authors.initials: B
authors.lastname: Descamps
authors.affiliation: Department of Electronics and Information Systems, IBiTech, MEDISIP, INFINITY, Ghent University, Belgium.
authors.forename: Christian
authors.initials: C
authors.lastname: Vanhove
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Belgium.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Remon
authors.affiliation: Department of Surgery, Ghent University Hospital, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Ceelen
authors.affiliation: Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Demetter
authors.affiliation: Laboratory of Experimental Cancer Research, Ghent University, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Bracke
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Belgium. Electronic address: br.degeest@ugent.be.
authors.forename: Bruno G
authors.initials: BG
authors.lastname: De Geest
authors.affiliation: Laboratory of Experimental Cancer Research, Ghent University, Belgium. Electronic address: olivier.dewever@ugent.be.
authors.forename: Olivier
authors.initials: O
authors.lastname: De Wever
mesh_terms: D000818:Animals; D032701:Biomimetics / Q000379:methods*; D002450:Cell Communication; D045744:Cell Line, Tumor; D005260:Female; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000473:pathology*; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D010534:Peritoneal Neoplasms / Q000473:pathology* / Q000517:prevention & control / Q000556:secondary*; D059016:Tumor Microenvironment
keywords: Biomimetic trap; Cancer-associated fibroblasts; Cell adhesion; Microencapsulation; Peritoneal metastasis; Tumor-environment