this research article is titled "dclk1 distinguishesbetween tumor and normal stem cells in the intestine" it was published by the chiba labat kyoto university in kyoto japan in nature genetics in january 2013. when you think about cancer, you probablythink about the tumor cell mass. and it is indeed this cell mass that causes damage tothe body. cancer forms when a group of cells (here in green) divides uncontrollably toproduce "differentiated" cells (here in purple) that no longer divide. these green dividingcells and these purple differentiated cells form the tumor. and it is this tumor cellmass that we try to destroy with treatments such as chemotherapy. however, to developeffective treatments, it's necessary for us
to understand where the tumor mass came from,where do these green dividing cells come from and how did they get there? some scientistshave hypothesized that some cancers but not all may be fueled by cells that resemble stemcells, which we call cancer stem cells, whereby a few slowly dividing cells produce thesegreen cells that will divide at a very high rate to make the tumor. other scientists thinkthat the cells that are fueling the tumor are the green ones that divide very rapidlyand that there are no slowly dividing cancer stem cells. stem cells (both normal and cancer stem cells)have a few important characteristics: unlike normal cells, stem cells :
- divide indefinitely - can make more of themselves as well as - make non stem cells so they are responsible for populating tissuesand repopulating tissues in case of injury. some cancers (such as leukemias, breast, colon,pancreas cancers)have been found to contain such cancer stem cells. so what does thismean for therapy? most cancers are treated with chemotherapy which kills cells that divideand make more cells. well, chemotherapy would efficiently killthe green dividing cells and eventually the purple differentiated cells since they wouldnot be replenished by the green cells. but
chemotherapy would not do a very good jobat killing the cancer stem cells since they don't divide very quickly. so the cancer stemcells would be resistant to chemotherapy. so as you can see, a cancer that is fueledby cancer stem cells may initially respond to chemotherapy but eventually the tumor wouldreappear due to the perseverance of cancer stem cells. so to treat these types of cancers,it would be ideal to kill both the cells that compose the mass of the tumor as well as thecancer stem cells that fuel the tumor volume. the presence of these cancer stem cells insome cancers has been controversial among scientists because they are very rare andit is hard to distinguish them from normal stem cells. so scientists have been lookingfor a marker of cancer stem cells that would
distinguish them from normal stem cells, whichwe want to keep around. the scientists of this article focused ona protein called dclk1 that was thought to mark normal stem cells but was also foundin some cancer cells in the intestine. they were curious to see which intestinal cellscontain dclk1? so the scientists designed mice whose cellsturned blue when dclk1 was present and all future cells that this cell produced alsoturned blue. the scientists induced this blue color only for a short period of time to trackwhat happens to the cells. using this technique, scientists can determine where cells camefrom and if the cell is dividing, what kinds of cells it produces just by looking at whichcells turned blue. so the scientists focused
on the intestines of these mice. because thestem cells produce all of the cells that make up the intestinal tissue, if a stem cell containsdclk1 then the whole intestinal tissue will be blue and this blue color will persist becausethe stem cell keeps dividing and making more cells. but, on the other hand, if a differentiatedpurple cells contains dclk1, only those differentiated purple cells will be blue since they are notdividing so no other cells in the intestine will be blue and the blue color will not persistbecause the differentiated cell does not divide and will eventually die off. so the questionis: which cells will turn blue and will the blue color persist? so in a normal tissue, the scientists foundthat the cells that turned blue from dclk1
presence were all of the differentiated cellsrepresented in purple that did not divide and the blue color did not persist. this meansthat in normal tissue, dclk1 is not present in stem cells, but in differentiated purplecells. next, the scientists wondered what kinds ofcells contained the dclk1 protein in intestinal cancer. so they performed the same experimentlooking at cells that contained dclk1 in a mouse that spontaneously develops intestinalcancer. in those tissues, over time, more and more of the tumors turned blue until allof the tumors were blue! and importantly, the tumors stayed blue for over 110 days!this suggested that dclk1 was present in some stem cell population that kept dividing andpersisted over time. because the normal tissue
around the tumor was not blue after 110 days,this meant that these stem cells were specific to the cancer and were not present in normaltissue!! they studied these dclk1 cells a little closerand confirmed that they were dividing and were present at the same position as normalstem cells but were only found in cancer tissue. these tumor dclk1 cells also contained markersof stem cells and other stem cell characteristics: -they could divide indefinitely - they could make more of themselves & producedifferentiated purple cells of the intestine so all of this information pointed to thefact that dclk1 might be a marker of cancer stem cells but not normal stem cells!
if this is true, then killing dclk1 cellsshould be able to kill off the tumor because we would be killing the cells that fuel thetumor. so the scientists did just that. when they specifically killed dclk1 cells usinggenetic approaches in the mouse with intestinal cancer, the tumors shrunk until there wasalmost no tumor left. but the normal tissue was for the most part normal since the normalstem cells are able to divide and repopulate the intestinal tissue. so what did this study show? this study showed that a protein "dclk1" playstwo different roles in normal and cancer tissues: in a normal tissue, dclk1 is present in thedifferentiated cells that do not divide.
however, in a cancer, dclk1 is present specificallyin cancer stem cells because dclk1 is not present in normal stemcells, killing dclk1 cells, shrinks and in some cases eliminates the tumor without affectingthe normal surrounding tissue! so what does this mean for you? this study supports the existence of thesecancer stem cells in intestinal cancer and, even though much work needs to be done toconfirm this finding in a human as well as in other cancers , this article provides apromising therapeutic opportunity to target these cancer stem cells! the next questionwill be: how do we kill dclk1 cells? the authors of this study used genetic manipulation inmice which is not feasible in humans. so the
next step will be to find a non invasive wayof delivering a drug specifically to dclk1 cells, or targeting them some other way. also,it will be important to understand where these cancer stem cells come from? do they comefrom differentiated cells or do they come from normal stem cells? by broadening our understanding of stem cellsand the presence of cancer stem cells in a variety of cancers, scientists are tryingto understand not just a static picture of a cancer but where it came from, how it gotthere and where it is likely to go as the cells continuously evolve and change!
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