TTP Labtech, Phenotypic Screening - 13

PHENOTYPIC SCREENING an e-Book Series Cellular Models for Finer Screening

In assays run by Janssen Research and Development, cMET but
not EGFR inhibitors reduced cell migration in hepatocyte growth
factor (HGF)-stimulated lung tumor spheroids. As shown in these
representative images, crizotinib inhibits cell migration pathways in
HGF-stimulated lung tumor spheroids. Day four 3D lung spheroids
were treated with crizotinib or compound in the presence of 20 ng/
mL of HGF for 48 hours to stimulate cell migration pathways. Total
area of migrating and spheroid were determined by using bright-field
images in a high-throughput Operetta high-content imaging system
(PerkinElmer). Magnification: 2× objective.

regulate pathways controlling cell proliferation,
polarity, and differentiation. As a result, effects that
a drug candidate might have in the context of such
gradients might not be apparent until the drug is
tested in vivo. One solution to this issue is the use of
3D hanging drop spheroids, in which cells suspended
in a droplet settle at the apex of the droplet and
establish appropriate cell-cell interactions.
Collagen Contraction
"The major advantage of using 3D spheroids
13 | GENengnews.com

over 2D monolayer cultures as a drug discovery
model is that its geometry and avascular nature
mimics the transport barrier of native tissue, where
drugs and other molecules experience diffusion
limitation, as they get farther away from blood
vessels," said Shiuchi Takayama, Ph.D., professor
of biomedical engineering at the University of
Michigan.
"The gradients that are established in the cellular
microenvironments in the 3D spheroids produce
drug response profiles that more closely resemble

in vivo responses compared to flat, 2D monolayer
cultures," Dr. Takayama added. Collagen contraction
is one of the processes by which cells remodel the
surrounding extracellular matrix, which is known to
be an important feature of disease progression.
Dr. Takayama's group has developed a 3D
spheroid-based collagen contraction assay that,
by miniaturizing the conventional 2D assay, more
closely models in vivo diffusion of nutrients and
soluble cues. In addition, the assay is more
amenable to the high throughput required for


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TTP Labtech, Phenotypic Screening

Table of Contents for the Digital Edition of TTP Labtech, Phenotypic Screening

Contents
TTP Labtech, Phenotypic Screening - 1
TTP Labtech, Phenotypic Screening - 2
TTP Labtech, Phenotypic Screening - 3
TTP Labtech, Phenotypic Screening - Contents
TTP Labtech, Phenotypic Screening - 5
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