Biomedical & Pharmacology Journal, September 2019.

Vol. 12(3), p. 1403-1416

CD133 and CD166 Expression Predicting the Possibility

of Prostatic Cancer Development in Cases of BPH

Khalida I. Noel1*, Mustafa M. Ibraheem1, Basim S. Ahmed2,

Ahmed F. Hameed1, Nibras H. Khamees1 and Sameh S. Akkila1
1
Department of Human Anatomy, College of Medicine, Mustansiriyah University, Baghdad, Iraq.
2
Department of Pathology, College of Medicine, Mustansiriyah University, Baghdad, Iraq.
*Correspond to Dr. Khalida Noel, Email: [email protected]

http://dx.doi.org/10.13005/bpj/1769

(Received: 18 June 2019; accepted: 06 September 2019)

Benign and malignant prostatic diseases are generallywell-known in the world.

Accordingly, this research is planned to assess the immunohistochemicalanalysis of CD133
and CD166 in the prostatic epithelium in samples of benign prostatic hyperplasia (BPH) and
normal looking epithelium around prostatic adenocarcinoma samples (PCa) and to explore the
opportunity of malignant alterations in benign tissue. The prostate samples were divided into
2 groups; 50 BPH samples, and 50 normally looking tissue surrounding prostatic carcinoma
samples (NPCA). The samples were treated for immunohistochemicalexamination of CD133 and
CD166. Over expression of CD133 appeared in the BPH group which was statistically significant
as compared to NPCA group. Conversely, over expression of CD166 stem cell marker in NPCA
group than BPH group as it was significant statistically. CD166 is a stem cell marker for tissue
tumorigenicity, while the positive expression of CD133 is not of value for cancer initiation.

Keywords: Immunohistochemistry, CD133, Prostatic cancer, BPH, CD166.

Prostate is a male exocrine gland, and a as metabolic syndromes, genetics and lifestyle.
portion of the male reproductive system1. The adult BPH is not supposed to be a straight risk factor
human prostate tissue weighs roughly 20 g, and is or a pre-cancerous period in prostate cancer5,
3 cm in length, 4 cm in width, and 2 cm in depth2. but there are countless genetic, hormonal, and
The prostate expands with age of men; prostate inflammatory causes have all been shared to be
enlargement is also related with appearance of known pathophysiological dynamic mechanisms
benign prostatic hyperplasia (BPH) 3. Prostate for the growth of both BPH and prostatic carcinoma
carcinoma is one of the veryprevalenttumor in (PCa), thus connecting these diseases together. Yet,
malesof developed countries. There were 1.3 on a cellular and molecular level, till now there is
million newlydiagnosed cases in 20184. no revision shown that the change of BPH tissue
BPH is a chronic illnessdescribed by has later transformed into an oncological ailment
prostatic enlargement, which manifestedas lower which is the core of the aims of this inquiry.
urinary tract disorders3. There are numerous factors Furthermore, the particular pathways of these
which can effectfor the development of BPH, such prostatic diseases have yet to be fully assumed. This

This is an Open Access article licensed under a Creative Commons license: Attribution 4.0 International (CC-BY).
Published by Oriental Scientific Publishing Company © 2019
1404 Noel et al., Biomed. & Pharmacol. J, Vol. 12(3), 1403-1416 (2019)

is crucial to enhance future management strategies Methods

for both diseases6.
Using stem cell markers like CD133 and Patients
CD166 can give a hint about the performance The present work was enrolled during the
of the epithelial cells of prostatic gland in both period extended from February 2018 to March 2019
BPH and normally looking tissue surrounding in Al- Yarmouk teaching hospital (histopathology
prostatic carcinoma, which specify that these unit) and two private histopathological labs. The
cells have a stem cell-likecomportment. The study was conducted on human prostatic tissue
presence of CD133+ cells suggested that a high specimens received from patients attending the
quantity of these tumor cells related to early lymph abovementioned hospital and labs.
node metastasis, advanced cancer stages, and A total number of 100 specimens were
more poorly differentiated cancers7,8. Whereas, selected for the study, some were prospective, with
the expression of CD166 by prostate stem a majority of retrospective samples obtained from
cellsproposethe possibility of using this cell surface archives of histopathology units of those labs and
molecule in targeted therapies of human prostate hospital.
tumors9. The specimens were divided as follows
Aims of the study Fifty primary prostatic carcinoma tissue
This researchdirected to estimate the samples were obtained from surgical resection
behavior of benign prostatic hyperplasia and the of the prostate,biopsy was taken from normal
likelihood ofalteration to cancerous lesion which tissue adjacent to the primary prostatic carcinoma
requisite follow up later. In addition, to consider the (NPCA)(normal samples e” 5 cm distant from
role of the immunohistochemical (IHC) reaction the cancer)10 and fifty tissue samplesof benign
types of glandular epithelium in normal tissue prostatic hyperplasia (BPH) were obtained from
adjacent to prostatic carcinoma by using CD133 transurethral resection surgery.
and CD166 markers as analyst to aid in choosing Patients were divided into two groups
the best management for prostatic carcinoma. (table 1), according to case type, namely normal
Finally, to compare the expression pattern of these adjacent to cancer including 50 patients proved to
markers in normal tissue adjacent to cancer and have prostatic adenocarcinoma, their age ranged
benign prostatic hyperplasia. from 55-82 years with mean age 70 years.The

Table 1. Group categories by type and number

Group Type Age (years) Mean age No. of patients Percentage

I BPH 60- 86 71 50 50%

II NPCA 55-82 70 50 50%
Total 100 100%

Table 2. Samples & marker type in relation to

staining intensity (chi square)

Staining Sample Type p-value

Intensity  NPCA BPH
  CD133 CD166 CD133 CD166

0 0% 8% 0% 46% 0.000
1+ 56% 8% 18% 48%
2+ 32% 36% 38% 6%
3+ 12% 48% 44% 0%
 Noel et al., Biomed. & Pharmacol. J, Vol. 12(3), 1403-1416 (2019) 1405

second 50 patients had BPH and their age range anti-CD133 antibody (Primary antibody from
between 60-86 years with mean age 71 years. Abnova,EntrezGeneID 8842, Code PAB12663).
Ethical approval for the study was The third section was treated with anti-CD166
obtained from the ethical board of Al-Yarmouk antibody (Primary antibody from Abnova, Clone
teaching hospital. The pathological diagnosis of 10F1G12, Code MAB10485).Secondary antibody
prostatic carcinoma was confirmed by reviewing detection kit (Abcam, code ab64261, rabbit specific
a freshly prepared hematoxylin and eosin stained HRP/DAB)was used.
slides. Formalin fixed samples and paraffin
Immunohisto chemistry implanted tissue sections were dewaxed using
For each sample, 3 serial sections were xylene, and progressively hydrated. Antigen
taken, each with 4 micrometers thickness.The retrieval was done by pressure cooking using citrate
first serial section was placed on an ordinary buffer for 20 minutes.The primaryanti-CD133 and
slide and stained byhematoxylin/eosin stain anti-CD166 antibodies were diluted 1:200 using
to confirm the diagnosis and to determine the abackground reducing dilution buffer (Abcam,
histological types and grades for the tumor. The code ab64211) and kept warm at room temperature
second section was placed on positively charged for 30 minutes.
slide for immunohistochemical staining with

Fig. 1. Staining intensity distribution of IHC markers according to prostatic disorder.

***= p-value < 0.001

Fig. 2. Staining percentage of IHC markers according to prostatic disorder.

*= p-value < 0.05
1406 Noel et al., Biomed. & Pharmacol. J, Vol. 12(3), 1403-1416 (2019)

Detection performedbylabeled Staining intensity was scored: 0 (no

streptavidin-biotin from Abcam secondary staining), 1+ (weak), 2+ (moderate) and 3+
detection kit, followed by DAB and chromogen (strong).
staining. The slides were quicklycounterstained Extent of staining (percentage) was
with hematoxylin, hydrated and mountedby DPX11. categorized by percentage: 0 = nil, 1= < 10 % of
Evaluation of the immunohisto chemical cell stained positively, 2= 10-50 %, 3= 51-80 %,
staining 4= > 80 %
For CD133, all tissue samples of NPCA, Statistical analysis
and BPH were assessed without prior knowledge, Statistical analysis was performed
and correlated with the age of the patient. It showed by using the SPSS – (Statistical Packages for
both cytoplasmic and membranous staining with Social Sciences) V18 .Categorical variables were
more pronounced membranous and nuclear evaluated by measuringthe percentage, mean, and
staining in some of the samples. range (min-max values). The qualitative data were
Evaluation of anti-CD166 antibody, all verified using Pearson Chi–square test (X2 –test),
tissue samples of NPCA, and BPH were assessed and independent sample t-test.
blindly, and interrelated with the age of the patient.
It showed both cytoplasmic and membranous Results
staining with more pronounced membranous
staining12,13. Comparison of IHC marker expressions
Staining percentage and intensity for of CD133 and CD166 according to sample type:
CD133 and CD166 were calculated as follows14,15: Regarding the intensity of markers

Table 3. Sample & marker type in relation to Table 4. Sample & marker type in relation to total
staining percentage (t-test) score (t-test)

Sample IHC Staining percentage  P-value Sample IHC Total Score p-value
Type  Marker Mean SD Type Marker Mean SD

BPH CD133 78.7% 18.9% 0.019 BPH CD133 1.86 0.8 0.013
  CD166 29.1% 13.7%     CD166 0.35 0.19
NPCA CD133 48.6% 3.5% 0.027 NPCA CD133 0.86 0.78 0.031
  CD166 83.6% 7.5%     CD166 2.08 0.9

Fig. 3. Total score of IHC marker staining according to prostatic disorder.

*= p-value < 0.05
 Noel et al., Biomed. & Pharmacol. J, Vol. 12(3), 1403-1416 (2019) 1407

staining and by using Pearson’s Chi-square test. was significantly different for the markers in each
In the BPH group, CD133 had the most intense prostatic disorder. In the BPH group, CD133
response (3+, 44%) and none of the samples had a was the mostly expressed marker in comparison
(0) response, while CD166 had the least response to CD166 (p-value=0.019). In the NPCA group,
(1+, 48%) and none of the samples had a (3+) CD166 was the mostly expressed marker in
response (fig. 4, fig. 5, fig. 6, fig. 12, fig. 13, fig. 14). comparison to CD133 (p-value=0.027). CD133
In the NPCA group, CD166 had the most intense was significantly more expressed in BPH group
response (3+, 48%) while the negative response compared to NPCA group while CD166 had the
was only 8%. On the other hand, 56% of cases in opposite expression as shown on table 3 and
NPCA group obtained weak expression (1+) of figure 2.
CD133, but 0% of cases reflected the negative (0) The differences in total score of IHC
expression of CD133 (fig. 8, fig. 9, fig. 10, fig. 15, marker expressions was assessed by t-test, and there
fig. 16, fig. 17, fig. 18). Significant difference were was a statistical significance of different markers
obtained in between the two groups and markers according to prostatic disorder. CD133 had the
as p-value= 0.000 (table 2 and figure 1). highest score in the BPH group in comparison to the
For comparison of percentage of marker NPCAgroup and the other marker (p-value=0.013).
staining and by using t-test, the staining percentage In the NPCA group, CD166 had the highest

Fig. 4. Immunohistochemical expression of CD133 Fig. 5. Immunohistochemical expression of CD133 in

in BPH sample show 1+ staining (weak membranous BPH sample show 2+ staining (moderate membranous
staining) of CD133 (black arrows). X400 & cytoplasmic staining) of CD133 (black arrows). X400

Fig. 6. Immunohistochemical expression of CD133 in Fig. 7. Immunohistochemical expression of CD133

BPH sample show 3+ staining (strong membranous & in BPH sample show 1+ staining (weak membranous
cytoplasmic staining) of CD133 (black arrows). X400 &cytoplamic staining) of CD133 with nuclear
involvement (black arrows). X400
1408 Noel et al., Biomed. & Pharmacol. J, Vol. 12(3), 1403-1416 (2019)

scores compared to the other marker in the same BPH than in NPCA group and was significant
group and the same marker in the BPH group as statistically. Also, CD133 expressed more intensely
p-value=0.031 (table 4 and figure 3). in BPH group than NPCA group and was also
CD133 was expressed clearly in the cell statistically significant. As a result, the total score
membrane and cytoplasm of prostatic cells in both of expression of CD133 showed statistically
groups, in addition a few cases appeared with significant higher levels in BPH group than
nuclear association in BPH and NPCA groups as NPCA group. On other hand, 44% of samples in
appeared in fig. 7 and fig. 11. While CD166 was BPH group showed strong expression of CD133,
appeared in cell membrane and cytoplasm of the whereas, 56% of NPCA group samples showed
cells in both groups. weak appearance of CD133 stem cell marker. These
finding are in agreement with other researchers16,17.
Discussion All of these researchers showed the expression of
CD133 positive cells in the prostatic epithelial cells
Expression of CD133 in BPH and NPCA groups in benign18 and malignant status of the epithelium19
As appeared in our results, CD133 stem as well as in the normal looking epithelial tissues20.
cell marker had greaterstaining percentage in

Fig. 8. Immunohistochemical expression of CD133 in Fig. 9. Immunohistochemical expression of CD133 in

NPCA sample show 1+ staining (weak membranous NPCA sample show 2+ staining (moderate membranous
staining) of CD133 (black arrows). X400 and cytoplasmic staining) of CD133 (black arrows).
X400

Fig. 10. Immunohistochemical expression of CD133 in Fig. 11. Immunohistochemical expression of CD133 in
NPCA sample show 3+ staining (strong membranous NPCA sample show 2+ staining (moderate membranous
&cytoplamic staining) of CD133 (black arrows). X400 &cytoplamic staining) of CD133 with nuclear
involvement (black arrows). X400
 Noel et al., Biomed. & Pharmacol. J, Vol. 12(3), 1403-1416 (2019) 1409

CD133 was found to be expressed in other readings, using altered and novel anti-CD133
normal epithelial tissues of different organs such clones, have proposed that the appearance of
as the hematopoietic system21, the prostate22, the CD133 is not restricted to stem and progenitor
pancreas23, and the kidney24. cells 32,33and appears to be expressed in adult
Also CD133 is expressed in the benign epithelial tissue cells of mouse and human34,35.
epithelial conditions such as BPH18 and other According to our results, all samples of
benign conditions like benign tumors of skin both BPH and NPCA groups are CD133 positive
with apocrine differentiation19. In addition to the and no negative expression were obtained in both
expression CD133 in malignant conditions like groups. The explanations for these positivity is
breast cancer25, colorectal carcinoma26, bladder that: CD133 is a stem cell marker of normal,
carcinoma27 and prostatic cancer18. benign and malignant epithelial cells12, but the
Moreover, antibodies against CD133 have intensity of CD133 expression was different in
been designed for the separation and identification both groups. In BPH group; 44% of samples
of a putative populace of tumor initiating cells showed strong positivity, on the other hand, 56% of
or cancer stem cells (CSCs) in many of human samples in NPCA group expressed CD133 weakly.
carcinomas28,29, and in malignant melanoma30. The reason for this different positive intensity of
In glioma, the amplified number of CD133 expression is associated to differential attraction
positive cancer cells, in addition to the existence of the diverse antibodies to different glycosylated
of clusters of these cells, has been suggested as types of CD133. So the glycosylation may altered
a main prognostic factor, autonomous of other depending on the stage of cellular differentiation19,
featuressuch as tumor grade31. On the other hand, or it can be changed during the path of malignant
transformation 36. The other reason for over
expression of CD133 in BPH samples is correlated
to presence of inflammatory cell populations in
BPH samples17, which may be accompanying with
the hyperplastic changes37 and so the intensity
of staining is stronger than normal tissue around
cancer in NPCA group which appeared low as
explained by other researchers17. In contrast,
Miyazawa et al.,18 suggested that there were no
clear reason for the different staining intensity
between benign and cancer patients.
CD133 was latelyestablished to
undergo differential glycosylation in colon
Fig. 12. Negative immunohistochemical expression of
CD166 in BPH sample. X400

Fig. 13. Immunohistochemical expression of CD166 Fig. 14. Immunohistochemical expression of CD166 in
in BPH sample show 1+ staining (weak membranous BPH sample show 2+ staining (moderate membranous
staining) of CD166 (black arrows). X400 staining) of CD166 (black arrows). X400
1410 Noel et al., Biomed. & Pharmacol. J, Vol. 12(3), 1403-1416 (2019)

CSCs as paralleled with differentiated cancer node metastasis, advanced cancer stages and poorly
cells 38 . This occurrencewouldclarify some differentiated tumors40,41 and so exhibited resistance
conflictingexplanations that have been described to management and poor survival26. Conversely,
when the CD133 protein and mRNA expression other researchers clarified that the tumorigenic
designs were linked 39. As newlysuggested by potential did not exist in the CD133+ stem cells but
Kemper et al., differential glycosylation of the was constantlydetected in the CD133-populace42.
extracellular domain of CD133 can armor the These factsestablished that benign basal cells
epitope from recognition by IHC using the antibody contain cells of origin of prostate cancer and
CD13338. recommended that proliferative CD133- basal cells
CD133 was considered as a marker of are more vulnerable to tumorigenesisif compared
tumor initiating cells in many cancers25, one of to CD133+ stem cells43. Tumorigenic potential did
these cancers is the prostatic carcinoma. Based on not arise from positive CD133 stem cells; but might
these information, the tumor cells were allocated be appeared in the negative CD133 populace44.
in to CD133+ and CD133- cells, that CD133+ cells Certainly, The resistance of CD133 positive cells
showed stem like features26, while CD133- cells to chemotherapy were more than CD133 negative
did not. According to these data, the great number cells in glioma and hepatocellular cancer, proposing
of CD133+ tumor cells is related with early lymph CD133 as a probable marker of cancer stem

Fig. 15. Negative immunohistochemical expression of Fig. 16. Immunohistochemical expression of CD166
CD166 in NPCA sample. X400 in NPCA sample show 1+ staining (weak membranous
staining) of CD166 (black arrows). X400

Fig. 17. Immunohistochemical expression of CD166 in Fig. 18. Immunohistochemical expression of CD166 in
NPCA sample show 2+ staining (moderate membranous NPCA sample show 3+ staining (strong membranous &
& cytoplasmic staining) of CD166 (black arrows). X400 cytoplasmic staining) of CD166 (black arrows). X400
 Noel et al., Biomed. & Pharmacol. J, Vol. 12(3), 1403-1416 (2019) 1411

cells45,46. It has been displayed that prostate tumor would clarify the low CD166 appearance in normal
derived CD133 positive cells are displayingself- prostatic glands, which illustrate a very low level
renewaland widespread proliferationirrespective of of proliferation47. CD166 also appeared in the
the tumor grade16. These conclusionsconfronted the hyperplastic glands with weak intensity47.
existingacceptance that normal stem cells and cells CD166 is a tumor initiating and cancer
of origin of cancer are the similar cell type(s)42. stem cell markers 48 and it is up regulated in
Thorough studies need to be performed to learn prostatic carcinoma53, give the reason that when
more about the role of CD133 in PCa origination. addition of CD166;augmented sphere forming
Other researchers found that the activity in prostatic tumor cell lines and in human
significance of CD133 expression may be attenuated prostatic cancer specially castration resistant
by using it with other stem cell markers to confirm prostatic cancer (CRPC) samples43. Consequently,
the presence of stem cell like activity in prostatic CD166 may enhance both human prostate tissue
epithelial cells20. stem/progenitor cells and (CRPC) cells9. Prostate
Expression of CD166 in BPH and NPCA groups stem/progenitor cells function in glandular
Our results showed that the percentage development and preservation;they may be marks
of CD166 expression in the NPCA group was for tumor initiation, so classification of these cells
higher than BPH group with statistical significance. may be of therapeutic value54. Cells from detached
Additionally, the strong intensity of CD166 tissues that form spheres in vitro often characterize
staining was appeared in the NPCA group samples, stem/progenitor cells. A subclass of human prostate
were 48% of samples expressed3+ level of intensity cells that custom spheres are accomplished for
which was statistically significant as compared to self-renewal and tissue regeneration55.
BPH group with weak intensity (1+) for 48% of Normal human prostate comprises three
samples. As a result, statistically significant higher dissimilarsorts of cells, that is luminal secretory,
total score obtained in NPCA group as compared basal and neuroendocrine cells. Subsequently,
to BPH group. These results are agreed with the human prostate cancer is described by loss of basal
findings of other researchers47,48. cells and growth of luminal cells, numerous animal
CD166 expression is commonly existing models suggest that luminal specific progenitors are
in most epithelial tissues and related carcinomas49. the causes of initiating prostate cancer56. Though,
It is important in tumor development and invasion50. using the tissue regeneration methodology, basal
The molecular activity of CD166 is controlled cells have verified to be veryeffective oncogenic
through shedding of its extracellular domain51. targets for human prostate cancer initiation57,58.
CD166 has been mentioned in few Remarkably, Choi et al.confirmed that adult murine
revisions as a significant potential biomarker for prostate basal and luminal cells are self-sustained
prostatic carcinoma9, although it is functionally lineages that both of them canassist as oncogenic
and clinically connected to many other cancers in targets for prostate cancer initiation59.
the body48,52. In our results, this up regulation ad
According to Kristiansen et al.47; CD166 strong expression of CD166 in the normal
was usually expressed in normal prostatic epithelia tissue around prostatic cancer was obtained and
which showed a mainly membranous and weak this can be explained on the finding of Jones et
cytoplasmic staining of secretory cells with no al.that considered this normal tissue as a field
staining of basal cells and stromal appearance cancerization zone because of the molecular
was not detected, the staining was commonly alterations of the cells in the normal tissue adjacent
homogenous which conclude the cell adhesive to cancer and so express CD166 strongly and give
criteria of CD166 molecule. It involves both the the idea of presence of tumor initiating cancer
stem cells and progenitor populations which is a stem-like cell in this tissue or even they are a
likely function for CD166 to preserve the reliability cancer stem cells60. The explanations for this field
of the stem cell niche by preserving the epithelial effect was described by many researchers as that
microenvironment49. CD166 is commonlyelaborate tumor tissue and adjacent normal tissue61, both
in morphogenesis of tubular structures, regardless of them exhibited significant up regulation of
of endothelial or epithelial source. This mechanism proliferation related genes including transcription
1412 Noel et al., Biomed. & Pharmacol. J, Vol. 12(3), 1403-1416 (2019)

factors62, signal transducers and growth regulators all adenomas of the colon, which was reflected
and proposed that normal appearing prostate tissue to be precursor lesions. According to these
can experience genetic modifications in response to findings, further information and more molecular
or inexpectation of morphologic cancer63,64. This is investigations may be needed to confirm these
an important prognostic feature which determine findings. In addition, in murine models, CD166
the suggestion of increased CD166 appearance was upregulated in prostates after castration9. These
with human prostate cancer metastasis and CRPC records specified that the amounts of stem cells in
growth. Furthermore, CD166-high expressing primary tumors or the patient circulation can be
subpopulation involves prostate stem/progenitor applied to recognize patients likely to experience a
and cancer initiating cells9. relapse and for whom very aggressive management
However, Kristiansen et al., 2003 is required.
showed that CD166 is over expressed in low IHC Expression of CD133and CD166 in BPH
grade tumor but is down regulated in high grade and NPCA groups
tumor, This difference might be clarified by altered CD133 is a cell membrane marker44, but
biological characters of CD166 in cell adhesion also expressed in the cytoplasm of the cells69.Our
of different cancers65, another explanation for resultsshowed both cell membrane and cytoplasmic
this difference of CD166 expression was that appearance of CD133 in both BPH and CA group
glandular (low-grade) carcinomas precise CD166 of samples and this is agreed with the findings
at higher levels, perhapsreplicating ongoing growth of Huwaitet al.44. In addition to membranous
and tubulesdevelopment, however high-grade and cytoplasmic expressions of CD133, nuclear
cancersincreasingly wildness tubulesgrowth in involvement also appeared in the nuclei of prostatic
favor of cribriform, solid, or single-cell invasion cells in BPH and normal tissue around cancer in
designs47. Other reasons included CD166 mRNA the NPCA group. These results are similar to the
up regulation in low grade prostate cancer and findings of many researchersin breast cancer12,
progressive loss in high-grade lesions may be of lung cancer69, hepatocellular carcinoma70 and
important implication66. colorectal cancer71 respectively. The explanation
So CD166 have a very important of this nuclear expression is controversial.
prognostic effects on prostatic carcinoma treatment Cantileet al. and Huang et al.12,69hypothesized
and follow up. CD166 has also been recommended that nuclear localization of CD133 may be
to show a seriouspart in numerous human asign of poor prognosis in breast cancer and
carcinomas and play as a potential therapeutic lung cancer, as they recognized that surface
target for cancer initiating cells67, and may be for molecules, when travelling into the nucleus, can
a proper surface marker for upcoming targeted act as transcriptional regulators by interfering with
drug delivery68. Also can be applied to examine the molecular paths directly linked to the proliferation
efficiency of CD166 - mediated drug delivery to and differentiation of cancer cells. In contrast,
prostate cancer initiating cells in vivo, particularly Chen et al. and Lee et al.70,71 hypothesized that
during CRPC expansion9. cytoplasmic CD133 appearance was associated
The weak expression of CD166 in 48% of with poor prognosis, while nuclear CD133
samples of BPH may be of significant importance appearance was considerablyassociated with
in determining whether there were a tumor positive prognosis. No previous study explained the
initiating cancer stem-like cell or cancer stem cell nuclear expression of CD133 in BPH, but we must
in the hyperplastic tissue, Jiao et al.9supposed that take this nuclear expression of CD133 in some of
CD166 was focally appeared in the benign adult BPH cases on considerations that it might give us a
prostate, CD166 mightaugment sphere-forming hint for any transformation and cancer development
capability of benign primary human prostate cells risk, since some researchers demonstrated a
in vitro and encourage the formation of tubule- telomerase activity in BPH might change and
like organizationsin vivo. But,Weichertetal. 14 therefore would obtain similar characters like
hypothesized that over expression of CD166 is a those of normal looking cells around tumor and
prematureoccurrence in malignant cell alteration cancer cells and so the possibility of developing
in colon carcinogenesis, as it was established in cancer is present and follow up is needed72. So,
 Noel et al., Biomed. & Pharmacol. J, Vol. 12(3), 1403-1416 (2019) 1413

further studies are needed for examining CD133 2018: GLOBOCAN estimates of incidence
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