Transcript 曾益新院士 ：Cancer Stem Cells or Stem

Cancer Stem Cells or Stem-like
Cancer Cells in NPC?
Yi-Xin Zeng
Sun Yat-Sen University Cancer Center
A frequently asked question in clinical practice:
How can we predict the outcomes of
NPC patients (Stage II/III) without
visible tumors after regular
therapeutics?
In other words:
What causes cancer recurrence or
metastasis?
Cancer stem cells (CSCs)
Self-renewal
Differentiation
Chemoresistant & Radioresistant
Invasive & metastatic
Liang
Fig. 1
(Wicha
et et
al.,al.,2006)
Identification of the first CSC
(Bonnet et al., 1997)
CSCs from different types of cancer
Cancer
Marker(s) of CSCs
Acute myeloid leukemia
CD34+CD38-Thy-1-; CD47+
Breast cancer
CD44+CD24-/low;
Colon cancer
CD133+; Lgr5+
Glioma
CD133+; CD15+
Nasopharyngeal carcinoma
ABCG2 (Side Population)
Hepatocellular carcinoma
CD133+; CD90+; EpCAM
Melanoma
ABCB5+
Skin cancer (Mus muscular)
CD34+
The principle of side-population sorting
(Forbes et al., 2006)
(Wang et al., Cancer Research 2007)
Summary
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NPC cells are a population with heterogeneity
There is a sub-group of cell (SP) exhibited stemcell-like characteristics, such as proliferation, selfrenewal and differentiation, strong tumorigenesis
ability, resistant to chemotherapy.
Origins of CSC?
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Transformation of adult stem cells
Genomic instability of cancerous cells?
Genomic instability of NPC cells
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The chromosome numbers varied from 17 to
107
The size of nuclei differs from 5 to 58 mm
Loss function of p53 (genome guardian)
Mutations of Myc, etc
A series of structurally abnormal
chromosomes detected by CGH, LOH or
FISH
Chromosome loss and gain
LOH analysis at whole genome level
Chromosome 10
Chromosome 12
Chromosome 11
D10S249 24%(7/29)
D10S591 14%(6/44)
D10S189 19%(15/78)
D11S4046 8%(4/48)
D11S1338 11%(7/64)
D10S547 30%(6/20)
D11S902
D11S904
D11S935
D11S905
D10S1653 16%(12/73)
D10S548 13%(7/54)
D10S197 5%(3/55)
20%(13/66)
50%(12/24)
37%(21/56)
31%(10/32)
D12S1617 16%(9/57)
D12S345 28%(21/74)
D12S85
30%(17/57)
D10S208 19%(11/57)
D11S1314 18%(5/27)
D11S901 12%(5/43)
D11S4191 32%(24/75)
D11S987 20%(10/51)
D10S196 15%(10/66)
D10S1652 21%(8/38)
D10S537 14%(9/64)
D11S937 32%(21/65)
D11S898 27%(12/45)
D10S185
D10S192
9%(6/65)
10%(4/39)
D10S1693
D10S587
D10S217
D10S1651
D10S212
15%(8/52)
19%(15/77)
26%(10/39)
9%(3/34)
14.%(3/21)
Chromosome 13
D12S352
27%(6/22)
D12S99
23%(14/62)
D12S336
24%(17/70)
D12S364
20%(12/61)
D11S908 42%(18/43)
D11S925 29%(12/41)
D11S4151 21%(6/29)
D11S1320 27%(17/64)
D11S968 22%(20/91)
D12S368
29%(22/77)
D12S83
12%(9/77)
D12S326
D12S346
D12S78
D12S79
10%(5/50)
18%(12/65)
7%(4/60)
18%(10/55)
D12S86
D12S324
D12S1659
D12S1723
11%(7/66)
14%(7/49)
15%(5/34)
31%(9/29)
D14S283
D14S275
D14S70
D14S288
D14S276
23%(10/44)
D14S63 34%(17/50)
D14S258 41%(23/56)
D14S74 44%(8/18)
D15S1007
D15S1012
D15S994
D15S978
D15S117
D15S153
D15S131
18%(11/61)
21%(8/38)
20%(3/15)
11%(6/57)
9%(2/22)
12.%(7/58)
26%(14/54)
D15S205
D15S130
26%(3/14)
27%(11/40)
D15S120
12%(7/60)
D16S423
D13S153 32%(22/68)
D13S156
D18S59
D13S159 37%(20/54)
D13S158 18%(6/34)
D13S173 13%(8/61)
D13S1265 26%(7/27)
D13S285 24%(6/25)
D18S452
D18S464
12%(7/56)
4%(2/45)
D18S53
20%(10/49)
D17S849
D17S831
D17S938
D17S1852
D17S799
28%(16/58)
16%(10/64)
19%(13/70)
10%(7/70)
12.%(6/49)
13%(9/70)
D17S921 33%(20/61)
D17S1857 4%(3/71)
D16S3046 33%(13/39)
D16S3068 24%(11/46)
D16S3136 29%(18/62)
D17S1868 20%(17/83)
D16S415
D17S787
D17S944
23%(12/53)
Chromosome 20
18%(14/78)
10%(2/20)
D17S949
4%(3/77)
D17S785
17%(10/58)
D17S784
D16S516 33%(5/15)
D19S216
D19S884
16%(7/44)
25%(21/83)
D19S226 9%(7/80)
D20S117
D20S889
D20S115
D20S186
D20S112
13%(7/54)
D17S928 42%(13/31)
Chromosome 21
Chromosome 22
D18S1102 10%(8/77)
D18S474 19%(3/16)
D19S220
11%(9/81)
D19S420
D19S902
14%(11/80)
24%(13/55)
17%(11/64)
16%(8/53)
27%(13/49)
14%(7/50)
16%(12/76)
15%(11/72)
D19S418 44%(21/48)
D19S210
28%(17/61)
D22S420 11%(6/55)
25%(7/26)
15%(10/67)
21%(9/43)
17%(4/23)
9%(7/74)
21%(6/29)
D19S414
D18S68
D18S61
D18S1161
D18S462
D18S70
Chromosome 17
21%(13/61)
D18S63 34%(13/38)
D18S478
14%(7/49)
D13S170 32%(18/57)
D13S265 16%(4/25)
D16S3091 23%(16/69)
D16S520 22%(14/65)
Chromosome 19
29%(18/62)
D13S263 39%(32/82)
D16S3075 31%(18/58)
D14S65 44%(34/77)
D14S985 30%(14/47)
D14S292 40%(21/53)
Chromosome 18
24%(15/63)
D13S218
Chromosome 16
D15S128 9%(5/57)
D15S1002 23%(19/81)
52%(32/61)
34%(23/67)
43%(26/61)
36%(8/22)
23%(14/61)
D13S217
D13S171 35%(25/71)
Chromosome 14
Chromosome 15
D13S175
D20S195 18%(6/34)
D22S539 11%(4/38)
D22S315 9%(4/31)
D21S1256 21%(6/29)
D21S1914 9%(4/44)
D21S1252 36%(30/84)
D20S107 9%(5/64)
D22S280 11%(7/63)
D22S283 17%(12/72)
D22S423 10%(3/29)
D22S274
D20S119
D20S178
D20S196
D20S100
D20S173
D20S171
14%(10/73)
18%(8/45)
12%(6/50)
14%(8/57)
20%(8/40)
8%(5/61)
D21S266
18%(14/79)
0%(0/65)
Her2 overexpression in NPC
Sox2
GAPDH
(Liang et al., JBC 2009)
(Immunostaining of ABCG2)
(Genome-wide CNV analysis)
Summary
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“Stem-like” is changeable phenotype
Genomic instability results in formation of stemlike cancer cells
Cancer-initiating cells: CSC (transformed tissue
stem cells), transformation of progenitor or
differentiated cells
Stem-like cancer cells: cause of cancer recurrence
or metastasis
Thank you!