title: Multi-step microfluidic device for studying cancer metastasis.
abstract: This paper describes a multi-step microfluidic device for studying the deformation and extravasation of primary tumor cells. Prior to extravasation, primary tumor cells undergo sequential steps of deformation through the capillaries, before adhering and transmigrating through the endothelial lining and basement membrane. To study this cascade of events, we fabricated a multi-step microfluidic device whose microgaps were coated with Matrigel to mimic the basement membrane. The microchannel was lined with human microvascular endothelial cells (HMECs) to replicate the endothelial lining. Analysis of deformation, biological and migratory capabilities of various tumor cell lines viz. HepG2, HeLa, and MDA-MB 435S were quantified using the fabricated device. After deformation, the cells' viabilities were significantly reduced and their doubling times were simultaneously increased, indicating changes in their biological capability. However, cell deformation did not significantly reduce their cell motility. Cell motility was co-assessed using the cell's migration rate and the overall population's percentage migration under various conditions (no barrier, Matrigel and Matrigel-HMEC). The device was also used to quantify the effects of Matrigel and the endothelial lining on cell migration. Our results suggest that both played an independent role in inhibiting cell extravasation, with the Matrigel significantly slowing down cell movement and the endothelial lining reducing the total number of transmigrated cells.
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, #04-01, 138669, Singapore.
authors.forename: K C
authors.initials: KC
authors.lastname: Chaw
authors.forename: M
authors.initials: M
authors.lastname: Manimaran
authors.forename: E H
authors.initials: EH
authors.lastname: Tay
authors.forename: S
authors.initials: S
authors.lastname: Swaminathan
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D003094:Collagen / Q000737:chemistry; D004338:Drug Combinations; D042783:Endothelial Cells / Q000473:pathology; D006801:Humans; D007797:Laminin / Q000737:chemistry; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000473:pathology*; D011509:Proteoglycans / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen