PMID- 19435897
OWN - NLM
STAT- MEDLINE
DCOM- 20090708
LR  - 20220330
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 69
IP  - 10
DP  - 2009 May 15
TI  - The mechanical rigidity of the extracellular matrix regulates the structure, 
      motility, and proliferation of glioma cells.
PG  - 4167-74
LID - 10.1158/0008-5472.CAN-08-4859 [doi]
AB  - Glioblastoma multiforme (GBM) is a malignant astrocytoma of the central nervous 
      system associated with a median survival time of 15 months, even with aggressive 
      therapy. This rapid progression is due in part to diffuse infiltration of single 
      tumor cells into the brain parenchyma, which is thought to involve aberrant 
      interactions between tumor cells and the extracellular matrix (ECM). Here, we 
      test the hypothesis that mechanical cues from the ECM contribute to key tumor 
      cell properties relevant to invasion. We cultured a series of glioma cell lines 
      (U373-MG, U87-MG, U251-MG, SNB19, C6) on fibronectin-coated polymeric ECM 
      substrates of defined mechanical rigidity and investigated the role of ECM 
      rigidity in regulating tumor cell structure, migration, and proliferation. On 
      highly rigid ECMs, tumor cells spread extensively, form prominent stress fibers 
      and mature focal adhesions, and migrate rapidly. As ECM rigidity is lowered to 
      values comparable with normal brain tissue, tumor cells appear rounded and fail 
      to productively migrate. Remarkably, cell proliferation is also strongly 
      regulated by ECM rigidity, with cells dividing much more rapidly on rigid than on 
      compliant ECMs. Pharmacologic inhibition of nonmuscle myosin II-based 
      contractility blunts this rigidity-sensitivity and rescues cell motility on 
      highly compliant substrates. Collectively, our results provide support for a 
      novel model in which ECM rigidity provides a transformative, microenvironmental 
      cue that acts through actomyosin contractility to regulate the invasive 
      properties of GBM tumor cells.
FAU - Ulrich, Theresa A
AU  - Ulrich TA
AD  - Department of Bioengineering, University of California Berkeley and University of 
      California San Francisco/University of California Berkeley Joint Graduate Group 
      in Bioengineering, Berkeley, CA 94720-1762, USA.
FAU - de Juan Pardo, Elena M
AU  - de Juan Pardo EM
FAU - Kumar, Sanjay
AU  - Kumar S
LA  - eng
GR  - DP2 OD004213/OD/NIH HHS/United States
GR  - DP2 OD004213-01/OD/NIH HHS/United States
GR  - 1DP2OD004213/OD/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20090512
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Fibronectins)
RN  - 9013-26-7 (Actomyosin)
SB  - IM
MH  - Actomyosin/*physiology
MH  - Animals
MH  - Cell Adhesion/physiology
MH  - Cell Division/physiology
MH  - Cell Line, Tumor
MH  - Cell Movement/physiology
MH  - Cues
MH  - Extracellular Matrix/*pathology/*ultrastructure
MH  - Fibronectins/physiology
MH  - Glioblastoma/pathology/physiopathology
MH  - Glioma/*pathology/*physiopathology
MH  - Humans
MH  - Muscle Contraction
MH  - Neoplasm Invasiveness
MH  - Stress, Mechanical
PMC - PMC2727355
MID - NIHMS105478
COIS- Conflicts of Interest: None.
EDAT- 2009/05/14 09:00
MHDA- 2009/07/09 09:00
PMCR- 2010/05/15
CRDT- 2009/05/14 09:00
PHST- 2009/05/14 09:00 [entrez]
PHST- 2009/05/14 09:00 [pubmed]
PHST- 2009/07/09 09:00 [medline]
PHST- 2010/05/15 00:00 [pmc-release]
AID - 0008-5472.CAN-08-4859 [pii]
AID - 10.1158/0008-5472.CAN-08-4859 [doi]
PST - ppublish
SO  - Cancer Res. 2009 May 15;69(10):4167-74. doi: 10.1158/0008-5472.CAN-08-4859. Epub 
      2009 May 12.