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2018 ; 8
(1
): 4608
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The mode and dynamics of glioblastoma cell invasion into a decellularized
tissue-derived extracellular matrix-based three-dimensional tumor model
#MMPMID29545552
Koh I
; Cha J
; Park J
; Choi J
; Kang SG
; Kim P
Sci Rep
2018[Mar]; 8
(1
): 4608
PMID29545552
show ga
Glioblastoma multiforme (GBM) is the most common brain tumor with very aggressive
and infiltrative. Extracellular matrix (ECM) plays pivotal roles in the
infiltrative characteristics of GBM. To understand the invasive characteristic of
GBM, it is necessary to study cell-ECM interaction in the physiologically
relevant biomimetic model that recapitulates the GBM-specific ECM
microenvironment. Here, we propose biomimetic GBM-specific ECM microenvironment
for studying mode and dynamics of glioblastoma cell invasion. Using tissue
decellularization process, we constructed a patient tissue-derived ECM
(pdECM)-based three-dimensional in vitro model. In our model, GBM cells exhibited
heterogeneous morphology and altered the invasion routes in a
microenvironment-adaptive manner. We further elucidate the effects of inhibition
of ECM remodeling-related enzymatic activity (Matrix metalloproteinase (MMP) 2/9,
hyaluronan synthase (HAS)) on GBM cell invasion. Interestingly, after blocking
both enzyme activity, GBM cells underwent morphological transition and switch the
invasion mode. Such adaptability could render cell invasion resistant to
anti-cancer target therapy. There results provide insight of how organ-specific
matrix differentially regulates cancer cell phenotype, and have significant
implications for the design of matrix with appropriate physiologically relevant
properties for in vitro tumor model.
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