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0007-4888/19/16740541--©-2019--Springer-Science+Business-Media,-LLC
Proliferative Activity of Colorectal Cancer Cells
with Different Levels of CD133 Expression
A. M. Gisina
1
, Ya. S. Kim
1
, D. M. Potashnikova
2
, A. V. Tvorogova
2
,
K. N. Yarygin
1
, and A. Yu. Lupatov
1
Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 2, pp. 84-89, June, 2019
Original article submitted November 30, 2018
We studied proliferative activity of colorectal cancer cells with different expression level of
CD133 molecule associated with cancer stem cells phenotype. Analysis of BrdU incorporation
into Caco-2 and HT-29 cell lines showed that the percentage of cells in the DNA synthesis
phase in the CD133
+/high
population is higher than in CD133
—/low
population. The expression
of proliferation marker Ki-67 and the percentage of Ki-67
+
cells were also higher in the
CD133
+/high
population. Colorimetric analysis with crystal violet dye showed that the number
of cells after 10-days culturing was higher in the CD133
+/high
population in both cell lines.
These findings suggest that cells with high level of CD133 expression are characterized by
higher proliferative activity, which can contribute to the tumor progression.
Key Words: CD133; cell proliferation; Caco-2; HT-29
1
V. N. Orekhovich Research Institute of Biomedical Chemistry;
2
M. V. Lo-
monosov Moscow State University, Moscow, Russia. Address for cor-
respondence: alisa.gisina@gmail.com. A. M. Gisina
Surface marker CD133 (prominin-1) is often used for
detection of cancer cells of many solid tumors [1,7].
Enhanced expression of this factor correlates with un-
favorable prognosis of the cancer disease [7]. Howev-
er, the function of this molecule remains little studied.
It is known that CD133 is predominantly located on
plasma membrane processes and microvilli, which in-
dicates possible involvement of this molecule in mem-
brane structure organization [4]. CD133 is directly
associated with cholesterol-containing lipid rafts and
therefore can be involved in various signal pathways
[9]. CD133 gene knockout determines a defect in the
formation of the outer segment of photoreceptor cells,
which leads to retina degeneration and blindness [10].
It was found that expression of CD133 is stimulated
by hypoxia in stem cells and in the tumor environment
[5]. There are data that CD133 is associated with Wnt/
β-catenin signaling pathway. In particular, deacetylase
HDAC5 physically interacts with CD133 in mamma-
lian cells. This interaction stabilizes β-catenin, while
inhibition of CD133 or HDAC5 leads to enhanced
acetylation and degradation of β-catenin, which cor-
relates with inhibition of cell proliferation in vitro
and suppression of the growth of tumor xenotrans-
plant [8]. It was demonstrated that CD133 through
interaction with Src-kinase followed by activation of
FAK signaling is involved into stabilization of EGFR,
inhibition of apoptosis, and stimulation of cell migra-
tion and metastasizing [6]. However, available data do
not fully describe the role of CD133
+
cells in tumor
populations.
In the present study we analyzed the relationships
between CD133 expression and proliferative activity
of colorectal adenocarcinoma cells.
MATERIALS AND METHODS
The study was performed on Caco-2 and HT-29
colorectal adenocarcinoma cells. The cells were grown
in DMEM/F-12 medium (PanEco) containing 10% fe-
tal calf serum (Gibco) at 37
o
C and 5% СО
2
. Cultured
cells were harvested by incubation with 25% trypsin
and Versene (1:1; PanEco) and washed with Hanks
saline (PanEco). CD133 expression was measured by
flow cytometry. To this end, the cells were stained
with primary labeled monoclonal antibodies to hu-
Cell Technologies in Biology and Medicine, No. 2, August, 2019
DOI 10.1007/s10517-019-04569-y