r***e
发帖数: 2539 | 1 上次和大家讨论cancer stem cell 或者cancer initiating cell的问题，受益匪浅。当
时我认为primary tumor中可能存在一小部分的CSC，但是通常用的limited dilution在
免疫缺陷老鼠中长瘤的的方法说服力不强。当时我举例说established cancer cell li
ne比如说HELA，做transplantation的话，也能看到类似的结果，而HELA细胞里难道也有
cancer stem cell吗？今天看到几篇文章，竟然就是从细胞株中分离CSC，他们的说法是
"An alternative approach for isolating stem cell populations is through enri
chment of side population (SP) cells, SP cells are identified by the capacit
y to efflux Hoechst dye"，就是说这些细胞能通过这个机制获得drung resistance。
http://cancerres.aacrjournals.org/content/67/10/4827
大家看看肿瘤细胞株真的也有CSC吗？感觉就是炒个概念，self-renew和drug resistan
ce就认为是CSC，有点牵强。大家怎么看？ |
t******y
发帖数: 716 | 2 我觉得很多细胞系，其实都是stem cell line，甚至我大胆推断（如果将来有人证明这
是对的，请记得给我credit）。能够自我更新的细胞都是干细胞。所以我们平常在用的
细胞系都应该归于此类，因此很多细胞系应该都是cancer stem cell。
为什么我要说能够自我更新的都是干细胞？因为从逻辑上讲，体内细胞最终的目是为了
完成某种功能，不敢说100%，绝大部分没有分裂能力的体细胞都是属于行使专一功能的
末端分化细胞。而那些能够自我更新的细胞，就没有必要既行使专一功能，又负担自我
更新的任务。因为从能量的合理利用上来说，劳动分工永远比多面手更有效率。
所以，那些能够自我更新的细胞就不是某端分化细胞。也就是说如果他能够分裂，必然
会继续分化，因此就具有“自我更新和分化能力”。 |
r***e
发帖数: 2539 | 3 你这个说法我不大认同。光能分裂应该不行吧，还要能分化成其他类型的细胞，才能说
stemness或者progenitor。
你说的是immortalized cell吧，大多数细胞株应该是。
你看下我原帖中的文章，也是说一部分细胞是stem cell like。
【在 t******y 的大作中提到】
: 我觉得很多细胞系，其实都是stem cell line，甚至我大胆推断（如果将来有人证明这
: 是对的，请记得给我credit）。能够自我更新的细胞都是干细胞。所以我们平常在用的
: 细胞系都应该归于此类，因此很多细胞系应该都是cancer stem cell。
: 为什么我要说能够自我更新的都是干细胞？因为从逻辑上讲，体内细胞最终的目是为了
: 完成某种功能，不敢说100%，绝大部分没有分裂能力的体细胞都是属于行使专一功能的
: 末端分化细胞。而那些能够自我更新的细胞，就没有必要既行使专一功能，又负担自我
: 更新的任务。因为从能量的合理利用上来说，劳动分工永远比多面手更有效率。
: 所以，那些能够自我更新的细胞就不是某端分化细胞。也就是说如果他能够分裂，必然
: 会继续分化，因此就具有“自我更新和分化能力”。
|
t******y
发帖数: 716 | 4 细胞为什么要分裂，不就是为了分化成功能细胞？
细胞不会无缘无故分裂。 |
W****C
发帖数: 1937 | 5
太不专业了
我不做stem cell的， 我等着看专业的讨论。。。
【在 t******y 的大作中提到】
: 细胞为什么要分裂，不就是为了分化成功能细胞？
: 细胞不会无缘无故分裂。
|
s******r
发帖数: 2876 | 6 细胞本来就应该分裂，yeast如此，bacteria也如此。
细胞为什么要分裂，不就是为了分化成功能细胞？
细胞不会无缘无故分裂。
【在 t******y 的大作中提到】
: 细胞为什么要分裂，不就是为了分化成功能细胞？
: 细胞不会无缘无故分裂。
|
t******y
发帖数: 716 | |
d****u
发帖数: 1553 | 8 细胞的分裂不仅是为了分化吧，还得维持器官稳定吧。 |
t******y
发帖数: 716 | 9 什么器官稳定？当然stem cell肯定是要占据一定组织空间的，如果这个算是功能，当
然也可以说，不过，细胞肯定不是为了仅仅占据空间。 |
p******d
发帖数: 3737 | 10 CSC这个概念看你怎么看。我觉得本身它是个毫无意义的概念，除非和临床结合。
临床上CSC的提出一部分原因是因为有一小部分的细胞对chemo有强烈的抵抗能力，在
chemo后导致
肿瘤的复发。这就和你说的sp细胞的概念扯上关系了，因为后来发现这些细胞表达的基
因例如
multiple drug resistant protein导致chemo drug被泵出了细胞外，导致了细胞对这
些药
物耐受，这也是sp细胞用来寻找各个组织干细胞的一个起源。
另外一个临床的原因是转移。很显然，转移的细胞导致新的肿瘤灶形成。这也是为啥
Weinberg实验
室会把CSC和EMT联系在一起了。
不论人类原发肿瘤本身或者建立的细胞系，在细胞表型上肿瘤常常是heterogeneous的
，病理上往
往要划定一定的百分比标准来判断是否某一标志物阳性，例如淋巴瘤的CD20或者乳腺癌
的ER受
体。还有关于你说的hela细胞，hela也是从人肿瘤里面分离出来的永生化细胞株。永生
化或者单克
隆筛选不等于获得的细胞株中每个细胞就在表型上完全一致。根据表面标志物来分，这
些细胞仍然
heterogeneous，尽管遗传背景完全一致。所以说在细胞株里面有tumor initiating细
胞或者
CSC本身我不觉得有问题。
这是我个人对这个方向的理解，有错误的请大家指正。
。当
li
也有
法是
through enri
capacit
resistan
【在 r***e 的大作中提到】
: 上次和大家讨论cancer stem cell 或者cancer initiating cell的问题，受益匪浅。当
: 时我认为primary tumor中可能存在一小部分的CSC，但是通常用的limited dilution在
: 免疫缺陷老鼠中长瘤的的方法说服力不强。当时我举例说established cancer cell li
: ne比如说HELA，做transplantation的话，也能看到类似的结果，而HELA细胞里难道也有
: cancer stem cell吗？今天看到几篇文章，竟然就是从细胞株中分离CSC，他们的说法是
: "An alternative approach for isolating stem cell populations is through enri
: chment of side population (SP) cells, SP cells are identified by the capacit
: y to efflux Hoechst dye"，就是说这些细胞能通过这个机制获得drung resistance。
: http://cancerres.aacrjournals.org/content/67/10/4827
: 大家看看肿瘤细胞株真的也有CSC吗？感觉就是炒个概念，self-renew和drug resistan
|
|
|
l******p
发帖数: 787 | 11 干细胞不是功能概念么，能行使相应功能的细胞就是干细胞，个人见解 |
p******d
发帖数: 3737 | 12 关键肿瘤的功能怎么定义呢？
【在 l******p 的大作中提到】
: 干细胞不是功能概念么，能行使相应功能的细胞就是干细胞，个人见解
|
l******p
发帖数: 787 | 13 我不做肿瘤，但涉猎过组织干细胞。目前体外组织干细胞群最有说服力的应当是生殖干
细胞和造血干细
胞，因为有强大的体内移植功能检测，比如不育的小鼠移植过后具有生殖能力。我猜肿
瘤的功能应当是
促使肿瘤发生，但不排除前体细胞也有此功能，所以说如果移植后能在体内产生肿瘤，
从而说一个群体
中含有肿瘤干细胞应当是安全的
【在 p******d 的大作中提到】
: 关键肿瘤的功能怎么定义呢？
|
l******p
发帖数: 787 | 14 你说的临床应当就是体内功能检测的意思吧
【在 p******d 的大作中提到】
: CSC这个概念看你怎么看。我觉得本身它是个毫无意义的概念，除非和临床结合。
: 临床上CSC的提出一部分原因是因为有一小部分的细胞对chemo有强烈的抵抗能力，在
: chemo后导致
: 肿瘤的复发。这就和你说的sp细胞的概念扯上关系了，因为后来发现这些细胞表达的基
: 因例如
: multiple drug resistant protein导致chemo drug被泵出了细胞外，导致了细胞对这
: 些药
: 物耐受，这也是sp细胞用来寻找各个组织干细胞的一个起源。
: 另外一个临床的原因是转移。很显然，转移的细胞导致新的肿瘤灶形成。这也是为啥
: Weinberg实验
|
t******y
发帖数: 716 | 15 说得很好。
【在 p******d 的大作中提到】
: CSC这个概念看你怎么看。我觉得本身它是个毫无意义的概念，除非和临床结合。
: 临床上CSC的提出一部分原因是因为有一小部分的细胞对chemo有强烈的抵抗能力，在
: chemo后导致
: 肿瘤的复发。这就和你说的sp细胞的概念扯上关系了，因为后来发现这些细胞表达的基
: 因例如
: multiple drug resistant protein导致chemo drug被泵出了细胞外，导致了细胞对这
: 些药
: 物耐受，这也是sp细胞用来寻找各个组织干细胞的一个起源。
: 另外一个临床的原因是转移。很显然，转移的细胞导致新的肿瘤灶形成。这也是为啥
: Weinberg实验
|
p******d
发帖数: 3737 | 16 我的理解是定义一个组织的干细胞有一些条件，例如1. 本身可以长期self-renewal，
也就是自我复
制；2. 可以有分化成为组织中功能细胞的能力，例如造血干细胞分化为白细胞红细胞
。这两点是组织干
细胞能保持组织homeostasis所必须的，也是一般终端分化细胞不具有的功能。
对于肿瘤，第一个标准应该差不多，但是第二个标准就比较困难。所以目前能做的就只
有细胞移植，看
能不能长出新的肿瘤。但是这个实验方法其实已经有些偏离了原来最初的本意，也就是
解决肿瘤复发和
转移的问题了。
【在 l******p 的大作中提到】
: 你说的临床应当就是体内功能检测的意思吧
|
h********n
发帖数: 4079 | 17 Why the concept of CSC is important in basic cancer research? To me, the
key question is: does a solid tumor (such as lung, liver, etc) arise from a
differentiated epithelial cell, or it arise from a tissue specific stem cell
/progenitor cell.
tissue specific stem cell/progenitor cell ---> differentiated epithelial
cell.
CSC--->differentiated cancer cells (with different potency).
Think of the comparison between these cells, especially the cancer vs normal
cells.
As to cancer cell lines, some of the cell lines are non-clonal lines so it
is possible there are some cell with higher tumorigenicity.
【在 p******d 的大作中提到】
: 我的理解是定义一个组织的干细胞有一些条件，例如1. 本身可以长期self-renewal，
: 也就是自我复
: 制；2. 可以有分化成为组织中功能细胞的能力，例如造血干细胞分化为白细胞红细胞
: 。这两点是组织干
: 细胞能保持组织homeostasis所必须的，也是一般终端分化细胞不具有的功能。
: 对于肿瘤，第一个标准应该差不多，但是第二个标准就比较困难。所以目前能做的就只
: 有细胞移植，看
: 能不能长出新的肿瘤。但是这个实验方法其实已经有些偏离了原来最初的本意，也就是
: 解决肿瘤复发和
: 转移的问题了。
|
h********n
发帖数: 4079 | 18 Another key question I would like to ask, if you think there is not enough
evidence showing CSC existing, what is the level of enough data?
If I say I isolate a population of cancer cells from a solid tumor in a
patient, and I show that these cells:
1. can differentiate to other types of epithelial-cancer cells (found in the
same tumor), which has their normal counterparts in normal tissue.
2. can self-renew.
3. when implanted to the same organ of healthy mice, it form a solid tumor,
and the potency of these group of cell is much higher than other group of
cancer cells from the original patient tumor.
4. the same experiment applied to same type of tumors from many patients.
Do you think this group of cell is CSC or tumor initiating cell?
If not, would you tell me more experiment you think necessary? |
s******r
发帖数: 2876 | 19 不过自从iPS发明以后，我觉得solid tumor也可能起源于分化细胞。
Why the concept of CSC is important in basic cancer research? To me, the
key question is: does a solid tumor (such as lung, liver, etc) arise from a
differentiated epithelial cell, or it arise from a tissue specific stem cell
/progenitor cell.
tissue specific stem cell/progenitor cell ---> differentiated epithelial
cell.
CSC--->differentiated cancer cells (with different potency).
Think of the comparison between these cells, especially the cancer vs normal
cells.
As to cancer cell lines, some of the cell lines are non-clonal lines so it
is possible there are some cell with higher tumorigenicity.
【在 h********n 的大作中提到】
: Why the concept of CSC is important in basic cancer research? To me, the
: key question is: does a solid tumor (such as lung, liver, etc) arise from a
: differentiated epithelial cell, or it arise from a tissue specific stem cell
: /progenitor cell.
: tissue specific stem cell/progenitor cell ---> differentiated epithelial
: cell.
: CSC--->differentiated cancer cells (with different potency).
: Think of the comparison between these cells, especially the cancer vs normal
: cells.
: As to cancer cell lines, some of the cell lines are non-clonal lines so it
|
p******d
发帖数: 3737 | 20 I guess these are two different concepts. CSC is to discuss if there are
some unique cells in the tumor that can self-renewal and give rise to
other tumor cells. The question you raised here is about the cell origin
of tumor, which is related with CSC, however not the same concept.Take a
look at this pape:
Crypt stem cells as the cells-of-origin of intestinal cancer.
Barker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H, van den
Born M, Danenberg E, Clarke AR, Sansom OJ, Clevers H.
Some people do favor the theory that tumors are originated from
stem/progenitor cells. However, as Sinister pointed out, the iPS cells
showed the dedifferentiation could happen. When comparing the
transformation risk of a small group of self-renewable, long-lived cells
vs. a vast larger group of shot-lived cells, I guess the answer is not
simple.
the
from a
stem cell
epithelial
normal
so it
【在 h********n 的大作中提到】
: Why the concept of CSC is important in basic cancer research? To me, the
: key question is: does a solid tumor (such as lung, liver, etc) arise from a
: differentiated epithelial cell, or it arise from a tissue specific stem cell
: /progenitor cell.
: tissue specific stem cell/progenitor cell ---> differentiated epithelial
: cell.
: CSC--->differentiated cancer cells (with different potency).
: Think of the comparison between these cells, especially the cancer vs normal
: cells.
: As to cancer cell lines, some of the cell lines are non-clonal lines so it
|
|
|
O******e
发帖数: 4845 | 21 现在CSC比较火的其中一个重要原因，是它给scientists和社会民众增加了攻克癌症的
新希望。很长一段时间，大家认为癌症太复杂根本不可能攻克，但现在有了Cancer
stem cells，那么你只要找到并杀死这些细胞，癌症就不会发生或者不会蔓延了。
这对我来说，更像是一个自欺欺人的美好愿望。我现在都还没被说服这个CSC的存在。
【在 p******d 的大作中提到】
: I guess these are two different concepts. CSC is to discuss if there are
: some unique cells in the tumor that can self-renewal and give rise to
: other tumor cells. The question you raised here is about the cell origin
: of tumor, which is related with CSC, however not the same concept.Take a
: look at this pape:
: Crypt stem cells as the cells-of-origin of intestinal cancer.
: Barker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H, van den
: Born M, Danenberg E, Clarke AR, Sansom OJ, Clevers H.
: Some people do favor the theory that tumors are originated from
: stem/progenitor cells. However, as Sinister pointed out, the iPS cells
|
h********n
发帖数: 4079 | 22 some ppl think differentied cell can de-differentiate back and then go
through tumorigenesis.
【在 s******r 的大作中提到】
: 不过自从iPS发明以后，我觉得solid tumor也可能起源于分化细胞。
:
: Why the concept of CSC is important in basic cancer research? To me, the
: key question is: does a solid tumor (such as lung, liver, etc) arise from a
: differentiated epithelial cell, or it arise from a tissue specific stem cell
: /progenitor cell.
: tissue specific stem cell/progenitor cell ---> differentiated epithelial
: cell.
: CSC--->differentiated cancer cells (with different potency).
: Think of the comparison between these cells, especially the cancer vs normal
|
h********n
发帖数: 4079 | 23 what do you think of my 2nd post?
【在 p******d 的大作中提到】
: I guess these are two different concepts. CSC is to discuss if there are
: some unique cells in the tumor that can self-renewal and give rise to
: other tumor cells. The question you raised here is about the cell origin
: of tumor, which is related with CSC, however not the same concept.Take a
: look at this pape:
: Crypt stem cells as the cells-of-origin of intestinal cancer.
: Barker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H, van den
: Born M, Danenberg E, Clarke AR, Sansom OJ, Clevers H.
: Some people do favor the theory that tumors are originated from
: stem/progenitor cells. However, as Sinister pointed out, the iPS cells
|
p******d
发帖数: 3737 | 24 I believe your second post represents the classic methodology used in the
CSC field and I would say that people would call these types of cells,
CSCs. However, CSC theory is only one theory. I am worried that we may
oversimplify the story...
【在 h********n 的大作中提到】
: what do you think of my 2nd post?
|
p******d
发帖数: 3737 | 25 是啊，人们和肿瘤的抗争已经很久了，失败太多成功太少。可能这就是从无机的物质中
获得有机的生命
的代价吧。谢谢楼主的包子：）能在这里和大家讨论真的特别开心：）
【在 O******e 的大作中提到】
: 现在CSC比较火的其中一个重要原因，是它给scientists和社会民众增加了攻克癌症的
: 新希望。很长一段时间，大家认为癌症太复杂根本不可能攻克，但现在有了Cancer
: stem cells，那么你只要找到并杀死这些细胞，癌症就不会发生或者不会蔓延了。
: 这对我来说，更像是一个自欺欺人的美好愿望。我现在都还没被说服这个CSC的存在。
|
h********n
发帖数: 4079 | 26 let's forget the theory or story. Let's forget CSC, either.
My question is: if you get a population of cells as I described, do you
think these cells are important? why or why not?
【在 p******d 的大作中提到】
: 是啊，人们和肿瘤的抗争已经很久了，失败太多成功太少。可能这就是从无机的物质中
: 获得有机的生命
: 的代价吧。谢谢楼主的包子：）能在这里和大家讨论真的特别开心：）
|
s*******3
发帖数: 3 | 27
。当
li
也有
法是
enri
capacit
resistan
【在 r***e 的大作中提到】
: 上次和大家讨论cancer stem cell 或者cancer initiating cell的问题，受益匪浅。当
: 时我认为primary tumor中可能存在一小部分的CSC，但是通常用的limited dilution在
: 免疫缺陷老鼠中长瘤的的方法说服力不强。当时我举例说established cancer cell li
: ne比如说HELA，做transplantation的话，也能看到类似的结果，而HELA细胞里难道也有
: cancer stem cell吗？今天看到几篇文章，竟然就是从细胞株中分离CSC，他们的说法是
: "An alternative approach for isolating stem cell populations is through enri
: chment of side population (SP) cells, SP cells are identified by the capacit
: y to efflux Hoechst dye"，就是说这些细胞能通过这个机制获得drung resistance。
: http://cancerres.aacrjournals.org/content/67/10/4827
: 大家看看肿瘤细胞株真的也有CSC吗？感觉就是炒个概念，self-renew和drug resistan
|
s*******3
发帖数: 3 | 28 CSC so far is only a concept. No convincing data were presented to prove it.
Sure, some cells in tumor popolation will be resistant to therapy. Are they
, however, CSC? For example, some tumor cells finally will be resistant to
target therapy and survive. These cells usually develop novel mutations in
the genes that target therapy acts on. In this case, these cells are
propably not CSC.
。当
li
也有
法是
enri
capacit
resistan
【在 r***e 的大作中提到】
: 上次和大家讨论cancer stem cell 或者cancer initiating cell的问题，受益匪浅。当
: 时我认为primary tumor中可能存在一小部分的CSC，但是通常用的limited dilution在
: 免疫缺陷老鼠中长瘤的的方法说服力不强。当时我举例说established cancer cell li
: ne比如说HELA，做transplantation的话，也能看到类似的结果，而HELA细胞里难道也有
: cancer stem cell吗？今天看到几篇文章，竟然就是从细胞株中分离CSC，他们的说法是
: "An alternative approach for isolating stem cell populations is through enri
: chment of side population (SP) cells, SP cells are identified by the capacit
: y to efflux Hoechst dye"，就是说这些细胞能通过这个机制获得drung resistance。
: http://cancerres.aacrjournals.org/content/67/10/4827
: 大家看看肿瘤细胞株真的也有CSC吗？感觉就是炒个概念，self-renew和drug resistan
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p******d
发帖数: 3737 | 29 I thought I was answering the questions in your second post, didn't I?
Of course I would think these cells are important! Why not? They are more
likely to be the cells that give rise to relapse and met if they are like
what you describe.
【在 h********n 的大作中提到】
: let's forget the theory or story. Let's forget CSC, either.
: My question is: if you get a population of cells as I described, do you
: think these cells are important? why or why not?
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t******y
发帖数: 716 | 30 ips 基本上从原代foreskin cell里来，而原来foreskin cell很有可能就是skin stem
cell。所以，ips的过程只是扩展了skin stem cell的分化潜能，而不是改变其分裂性
能。
a
cell
normal
【在 s******r 的大作中提到】
: 不过自从iPS发明以后，我觉得solid tumor也可能起源于分化细胞。
:
: Why the concept of CSC is important in basic cancer research? To me, the
: key question is: does a solid tumor (such as lung, liver, etc) arise from a
: differentiated epithelial cell, or it arise from a tissue specific stem cell
: /progenitor cell.
: tissue specific stem cell/progenitor cell ---> differentiated epithelial
: cell.
: CSC--->differentiated cancer cells (with different potency).
: Think of the comparison between these cells, especially the cancer vs normal
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s*******g
发帖数: 3332 | 31 de-differentiation在体内发现过么？我记得以前有过几篇paper，但都不令人信服
【在 h********n 的大作中提到】
: some ppl think differentied cell can de-differentiate back and then go
: through tumorigenesis.
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n********k
发帖数: 2818 | 32 well, csc or cell origin of cancer or whatever...nothing is important ot not
imprtant for that matter until it has
any clinical usage...I would just keep an open mind without thinking/
sticking too much of any camps so that it
limits my thinking....
【在 p******d 的大作中提到】
: 是啊，人们和肿瘤的抗争已经很久了，失败太多成功太少。可能这就是从无机的物质中
: 获得有机的生命
: 的代价吧。谢谢楼主的包子：）能在这里和大家讨论真的特别开心：）
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a****d
发帖数: 1919 | 33 。。。
not sure if you read the original iPSCs paper
can't agree with what you said
stem
【在 t******y 的大作中提到】
: ips 基本上从原代foreskin cell里来，而原来foreskin cell很有可能就是skin stem
: cell。所以，ips的过程只是扩展了skin stem cell的分化潜能，而不是改变其分裂性
: 能。
:
: a
: cell
: normal
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j***z
发帖数: 105 | 34 I still favor the old-school clonal evolution model of tumorigenesis. The
evidence for CSC so far are mostly correlative. For me the key experiment
would be:
If you selectively deplete the so-called "cancer initiating cells" without
affecting the bulk of the tumor, will you see the regression of tumor?
Unfortunately Weinberg's recent cell paper failed to address this.
For people who are interested this is a very good review:
Heterogeneity in Cancer: Cancer stem cells versus clonal evolution. 2009
Cell 138: 822-828 |
j***z
发帖数: 105 | 35 The experiments you described will convincingly show those cells are
sufficient to initiate tumor. I think we need a different set of experiments
to show they are "important".
【在 h********n 的大作中提到】
: let's forget the theory or story. Let's forget CSC, either.
: My question is: if you get a population of cells as I described, do you
: think these cells are important? why or why not?
|
h********n
发帖数: 4079 | 36 I don't think de-differentiation exist in nature or cause cancer
【在 s*******g 的大作中提到】
: de-differentiation在体内发现过么？我记得以前有过几篇paper，但都不令人信服
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h********n
发帖数: 4079 | 37 to initiate a tumor, many cancer cell lines are able to do it.
I am also thinking of what is "important".
Anyone has any thought?
experiments
【在 j***z 的大作中提到】
: The experiments you described will convincingly show those cells are
: sufficient to initiate tumor. I think we need a different set of experiments
: to show they are "important".
|
s*******g
发帖数: 3332 | 38 if they represent the origin of the tumor.
【在 h********n 的大作中提到】
: to initiate a tumor, many cancer cell lines are able to do it.
: I am also thinking of what is "important".
: Anyone has any thought?
:
: experiments
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r***e
发帖数: 2539 | 39 Yes, that's why I raised the question at the beginning. It seems that most o
f the cancer cell line can initiate tumor, but is there a sub-population in
these cell lines that acts like CSC?
As for what is important, in clinical? It's hard to tell. Say, cell origin o
f cancer is hot in basic field, but does this question help curing the cance
r in clinical?
【在 h********n 的大作中提到】
: to initiate a tumor, many cancer cell lines are able to do it.
: I am also thinking of what is "important".
: Anyone has any thought?
:
: experiments
|
h********n
发帖数: 4079 | 40 I would argue if you know the cellular origin of a cancer type, it would be
easier to find target.
Therapy does not come out from nowhere, it is from fruit of good basic
research 10-20 years ago. Think about anti-EGFR therapy, anti-angiogenesis
therapy, etc.
【在 r***e 的大作中提到】
: Yes, that's why I raised the question at the beginning. It seems that most o
: f the cancer cell line can initiate tumor, but is there a sub-population in
: these cell lines that acts like CSC?
: As for what is important, in clinical? It's hard to tell. Say, cell origin o
: f cancer is hot in basic field, but does this question help curing the cance
: r in clinical?
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|
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a*****g
发帖数: 543 | 41 Jumping to a deep water hole...
I would caution the widely "credited" potential of CSC(technically here refe
ring to the tumor-inititating cells identified in immune-deficient mice) ass
ociated with relapse, drug resistance and metastasis.
Can anyone point out an original research paper with some experimental data
showing these cells have any of the three major capabilities? My impression
is sadly none...But we read it everywhere...
Second, CSCs are defined vaguely. The standards mentioned by htscorpion, aka
, growing tumor in mice(at a single cell level) is really given by capabilit
y rather than identity. Speaking of identity, it appears there is no genetic
/epigenetic/FACS markers defining the same batch of functional validated CSC
s
So what can we ask about the CSCs(for a single disease) when each of them (f
rom the same tumor) does not share any molecular common feature?
Hope some CSC guy/girl can enlighten me on this...
【在 p******d 的大作中提到】
: I thought I was answering the questions in your second post, didn't I?
: Of course I would think these cells are important! Why not? They are more
: likely to be the cells that give rise to relapse and met if they are like
: what you describe.
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p******d
发帖数: 3737 | 42 I totally agree with you that some experiments focused too much on
transplantation and may have overlooked the clinical relevance. Just
like what I initially started, it is pointless to argue about the
identity of CSC if we are not aware of the real challenge in cancer
therapy (met and relapse).
Recent too papers in Cell may get closer to the core, both of which
focused on the epigenetic feature of CSC or chemoresistant cells.
Roesch et al, 2010
Sharma et al, 2010
With that said, I still believe the virtue of CSC study. Experiments are
experiments. The data never cheat you. It is just the theories that need
to be modified or revised.
here refe
mice) ass
data
impression
htscorpion, aka
capabilit
genetic
【在 a*****g 的大作中提到】
: Jumping to a deep water hole...
: I would caution the widely "credited" potential of CSC(technically here refe
: ring to the tumor-inititating cells identified in immune-deficient mice) ass
: ociated with relapse, drug resistance and metastasis.
: Can anyone point out an original research paper with some experimental data
: showing these cells have any of the three major capabilities? My impression
: is sadly none...But we read it everywhere...
: Second, CSCs are defined vaguely. The standards mentioned by htscorpion, aka
: , growing tumor in mice(at a single cell level) is really given by capabilit
: y rather than identity. Speaking of identity, it appears there is no genetic
|
j***z
发帖数: 105 | 43 Good point.
My guess is that within a tumor or even cell line, there is always a
population of cells with better tumorigenesis potential / drug resistance.
Even if you get rid of those cells, other cells will replace.
Since cell lines are supposed to be genetically identical, epigenetics might
play a role here. It would be very interesting to identify the factors
involved in generating such population of cells.
And in terms of curing cancer, personally speaking I think too much focus
has been placed on the genetics of cancer. Understanding the biochemistry
should be the key.
refe
ass
data
impression
aka
capabilit
genetic
【在 a*****g 的大作中提到】
: Jumping to a deep water hole...
: I would caution the widely "credited" potential of CSC(technically here refe
: ring to the tumor-inititating cells identified in immune-deficient mice) ass
: ociated with relapse, drug resistance and metastasis.
: Can anyone point out an original research paper with some experimental data
: showing these cells have any of the three major capabilities? My impression
: is sadly none...But we read it everywhere...
: Second, CSCs are defined vaguely. The standards mentioned by htscorpion, aka
: , growing tumor in mice(at a single cell level) is really given by capabilit
: y rather than identity. Speaking of identity, it appears there is no genetic
|
a*****g
发帖数: 543 | 44 It is interesting you mentioned the genetically similarity within cell line
s. Most of these studies would have been done using millions (if not billio
ns )of cells. The bias of sequencing or SNP would lead to identify the most
obvious low hanging fruit, such as KRAS, pten, p53 etc.
Apparently when single-cell level sequencing becomes widely available, iden
tifying subpopulations with genetic or epigenetic characteristics will be i
n a much better position.
http://www.genomeweb.com/sequencing/single-cell-sequencing-reveals-subpopul
ations-cancer-cells
I agree genetics(and epigenetics) has been emphasized for a long period in
cancer research. With our current knowledge, it is likely the mose conserve
d way to go after the disease. When you say biochemistry, do you mean metab
olism?
might
【在 j***z 的大作中提到】
: Good point.
: My guess is that within a tumor or even cell line, there is always a
: population of cells with better tumorigenesis potential / drug resistance.
: Even if you get rid of those cells, other cells will replace.
: Since cell lines are supposed to be genetically identical, epigenetics might
: play a role here. It would be very interesting to identify the factors
: involved in generating such population of cells.
: And in terms of curing cancer, personally speaking I think too much focus
: has been placed on the genetics of cancer. Understanding the biochemistry
: should be the key.
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w********r
发帖数: 1431 | 45 我觉得是炒概念。
cancer progenitor cell可能是有的，
但是非要说就是stem cell，就感觉有点奇怪了
。当
li
也有
法是
enri
capacit
resistan
【在 r***e 的大作中提到】
: 上次和大家讨论cancer stem cell 或者cancer initiating cell的问题，受益匪浅。当
: 时我认为primary tumor中可能存在一小部分的CSC，但是通常用的limited dilution在
: 免疫缺陷老鼠中长瘤的的方法说服力不强。当时我举例说established cancer cell li
: ne比如说HELA，做transplantation的话，也能看到类似的结果，而HELA细胞里难道也有
: cancer stem cell吗？今天看到几篇文章，竟然就是从细胞株中分离CSC，他们的说法是
: "An alternative approach for isolating stem cell populations is through enri
: chment of side population (SP) cells, SP cells are identified by the capacit
: y to efflux Hoechst dye"，就是说这些细胞能通过这个机制获得drung resistance。
: http://cancerres.aacrjournals.org/content/67/10/4827
: 大家看看肿瘤细胞株真的也有CSC吗？感觉就是炒个概念，self-renew和drug resistan
|
i*****i
发帖数: 30 | 46 significantly
我想说的是：任何细胞都有寿命，包括HSC CSC，所以CSC也不是一成不变的！
not
【在 n********k 的大作中提到】
: well, csc or cell origin of cancer or whatever...nothing is important ot not
: imprtant for that matter until it has
: any clinical usage...I would just keep an open mind without thinking/
: sticking too much of any camps so that it
: limits my thinking....
|
s******3
发帖数: 28 | 47 我觉得以后得用genom说话，表型也放一边，你说是cancer sc那他有什么基因标记？哪
个基因有问题啦？基因组的表观遗传有什么特殊？信号通路研究了这么多年，也没见什
么突飞猛进的进展。我觉得重点应该转移到细胞核里面去才对，从细胞核里面事情的差
异来说事，现在疾病和信号通路是单对多，或者多对多，而且超级不明白，一团浆糊的
状态，牛逼啦，你去转录水平说事，也弄个转录水平的疾病信号机制，但是转录似乎都
搞不明白是怎么回事。这么多年的科研，不知道方向到底该去哪里 |
t****p
发帖数: 1504 | 48 说到肿瘤的heterogeneicity，我来说点外行的想法。
就是说stem cell的概念不是绝对的，孤立的。所以人们引入了全能、多能的概念，又
引入progenitor,transient amplification cell的概念，目的是把连续的事件人为划
分为可描述的几个阶段。
相似的，在我看来找绝对概念的CSC是有问题的。一个肿瘤里面不应该只有两个细胞群
体，能重新形成肿瘤的csc和不能形成肿瘤的一般细胞，而是说每个细胞能形成肿瘤的
能力有高有低而已。所以，人们设想可以通过消灭一个肿瘤细胞中的特定细胞群来消灭
肿瘤的想法是误入歧途的。 |
b****r
发帖数: 17995 | 49 我的看法和你正好相反，细胞不一定要分裂，实际情况是，不分裂的细胞很快就死绝了
，你隔了一段时间后看到的都是会分裂的细胞的后代。如果所有细胞都没有获得分裂的
能力，那么你什么都不会看到，然后你会以为什么都没有发生。
【在 t******y 的大作中提到】
: 细胞为什么要分裂，不就是为了分化成功能细胞？
: 细胞不会无缘无故分裂。
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O******e
发帖数: 4845 | 50 Neurons都不分裂，能存活很长时间。动物体成年以后身体内的细胞大多处于终极分化
状态或休眠状态。
【在 b****r 的大作中提到】
: 我的看法和你正好相反，细胞不一定要分裂，实际情况是，不分裂的细胞很快就死绝了
: ，你隔了一段时间后看到的都是会分裂的细胞的后代。如果所有细胞都没有获得分裂的
: 能力，那么你什么都不会看到，然后你会以为什么都没有发生。
|
