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Increased Tissue Stiffness in Tumors from Mice with Neurofibromatosis-1 Optic Glioma.

Abstract
Children with neurofibromatosis type 1 (NF1) cancer predisposition syndrome are prone to the development of low-grade brain tumors (gliomas) within the optic pathway (optic gliomas). One of the key obstacles to developing successful therapeutic strategies for these tumors is the striking lack of information about the mechanical properties that characterize these tumors relative to non-neoplastic optic nerve tissue. To study the physical changes that may occur when an optic nerve glioma is present, we employed atomic force microscopy to measure the stiffness of healthy versus tumor-bearing optic nerve tissue. We found that the average elastic moduli of non-neoplastic and tumor-bearing optic nerves were ∼3 and ∼6 kPa, respectively. Based on previous studies implicating changes in extracellular matrix remodeling in other, related optic nerve pathological states, we found decreased expression of one major metalloproteinase protein (MMP-2) and unchanged expression of lysyl oxidase and a second metalloproteinase, MMP-9, in murine optic gliomas relative to normal non-neoplastic optic nerve. Collectively, these observations suggest a productive interplay between physical properties of mouse optic nerve gliomas and the extracellular matrix.
AuthorsChristopher Walter, Lindsey Crawford, Melinda Lai, Joseph A Toonen, Yuan Pan, Shelly Sakiyama-Elbert, David H Gutmann, Amit Pathak
JournalBiophysical journal (Biophys J) Vol. 112 Issue 8 Pg. 1535-1538 (Apr 25 2017) ISSN: 1542-0086 [Electronic] United States
PMID28445745 (Publication Type: Letter)
CopyrightCopyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Chemical References
  • Neurofibromin 1
  • RNA, Messenger
  • Protein-Lysine 6-Oxidase
  • Matrix Metalloproteinase 2
  • Mmp2 protein, mouse
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse
Topics
  • Animals
  • Disease Models, Animal
  • Elastic Modulus
  • Extracellular Matrix (physiology)
  • Matrix Metalloproteinase 2 (metabolism)
  • Matrix Metalloproteinase 9 (metabolism)
  • Mice, Transgenic
  • Microscopy, Atomic Force
  • Neurofibromatosis 1 (physiopathology)
  • Neurofibromin 1
  • Optic Nerve (physiopathology)
  • Optic Nerve Glioma (physiopathology)
  • Protein-Lysine 6-Oxidase (metabolism)
  • RNA, Messenger (metabolism)

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