title: Mechanical confinement triggers glioma linear migration dependent on formin FHOD3.
abstract: Glioblastomas are extremely aggressive brain tumors with highly invasive properties. Brain linear tracks such as blood vessel walls constitute their main invasive routes. Here we analyze rat C6 and patient-derived glioma cell motility in vitro using micropatterned linear tracks to mimic blood vessels. On laminin-coated tracks (3-10 μm), these cells used an efficient saltatory mode of migration similar to their in vivo migration. This saltatory migration was also observed on larger tracks (50-400 μm in width) at high cell densities. In these cases, the mechanical constraints imposed by neighboring cells triggered this efficient mode of migration, resulting in the formation of remarkable antiparallel streams of cells along the tracks. This motility involved microtubule-dependent polarization, contractile actin bundles and dynamic paxillin-containing adhesions in the leading process and in the tail. Glioma linear migration was dramatically reduced by inhibiting formins but, surprisingly, accelerated by inhibiting Arp2/3. Protein expression and phenotypic analysis indicated that the formin FHOD3 played a role in this motility but not mDia1 or mDia2. We propose that glioma migration under confinement on laminin relies on formins, including FHOD3, but not Arp2/3 and that the low level of adhesion allows rapid antiparallel migration.
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411 pascale.monzo@ifom.eu ms2001@columbia.edu.
authors.forename: Pascale
authors.initials: P
authors.lastname: Monzo
authors.affiliation: National Neuroscience Institute, Singapore 308433.
authors.forename: Yuk Kien
authors.initials: YK
authors.lastname: Chong
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Guetta-Terrier
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411.
authors.forename: Anitha
authors.initials: A
authors.lastname: Krishnasamy
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411.
authors.forename: Sharvari R
authors.initials: SR
authors.lastname: Sathe
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411 Department of Biomedical Engineering, National University of Singapore, Singapore 117575 Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228.
authors.forename: Evelyn K F
authors.initials: EK
authors.lastname: Yim
authors.affiliation: National Neuroscience Institute, Singapore 308433 Duke-NUS Graduate Medical School, Singapore 169857.
authors.forename: Wai Hoe
authors.initials: WH
authors.lastname: Ng
authors.affiliation: National Neuroscience Institute, Singapore 308433 Duke-NUS Graduate Medical School, Singapore 169857 Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597 Singapore Institute for Clinical Sciences, A*STAR, Singapore 117609.
authors.forename: Beng Ti
authors.initials: BT
authors.lastname: Ang
authors.affiliation: National Neuroscience Institute, Singapore 308433 Duke-NUS Graduate Medical School, Singapore 169857 Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore 169610.
authors.forename: Carol
authors.initials: C
authors.lastname: Tang
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411 Institut Jacques Monod, Université Paris Diderot and CNRS UMR 7592, 75205 Paris, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Ladoux
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411 National Neuroscience Institute, Singapore 308433.
authors.forename: Nils C
authors.initials: NC
authors.lastname: Gauthier
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411 Department of Biological Sciences, Columbia University, New York, NY 10027 pascale.monzo@ifom.eu ms2001@columbia.edu.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Sheetz
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena; D001932:Brain Neoplasms / Q000098:blood supply / Q000473:pathology*; D002448:Cell Adhesion; D002452:Cell Count; D054443:Cell Migration Assays / Q000379:methods*; D002465:Cell Movement; D000080865:Formins; D005909:Glioblastoma / Q000473:pathology; D005910:Glioma / Q000098:blood supply / Q000473:pathology*; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D051419:Paxillin / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D051376:Actin-Related Protein 2-3 Complex; C485994:FHOD3 protein, human; C579478:Fhod3 protein, rat; D000080865:Formins; D007797:Laminin; D008840:Microfilament Proteins; D009124:Muscle Proteins; D051419:Paxillin; C496063:Pxn protein, rat