The cancer stem cell theory suggests that tumors grow like normal tissues of the body, with stem cells at the starting point of an organized system that produces new cells to make a tissue grow. According to this idea, tumors contain:
Cancer stem cells that divide and feed tumour growth. These cells can self-renew (copy themselves) extensively, and also produce more mature cells called transit amplifying cells-..

Bulanin, D.

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Cancer stem cells in colorectal cancer Denis Bulanin, CLS, NU 2015 Outline 1. Anatomy of the colon 2. Stages of CRC 3. Crypt organization 4. Models of tumor development 5. Stem cells vs. CSC 6. Alternative strategies of cancer treatment P53 and P38/MK2 pathways 7. Current research 8. Future applications      Colorectal cancer (CRC) is the third leading type of cancer with 1,361,000 newly recorded cases in 2012, accounting for more than 694,000 deaths worldwide and the fifth in Kazakhstan 2500-3000 cases a year.  Anatomy of colon Stages of colorectal cancer Anatomy of the intestine Cell division takes place at the bottom of the crypt.  Cells move up the vilus and shed to the lumen Intestinal crypt organization 1. Enterocytes- absorption of nutrients, contain microvilli which increasing the surface area 2. Goblet cells – secretion of mucus 3. Enteroendocrine cells secret various hormones influencing gastrointestinal secretion or motility 4. Panneth cells – secrete anti-bacterial proteins into crypt lumen to protect the stem cells  Stem cells located  at +1 and + 4 positions At +1 CS are actively cycling At +4 SC slow cycling Current models for development of a tumor Fanali C., et al., World J Gastroenterol. 2014 Jan 28; 20(4): 923–942. Stem cell vs. Cancer stem cell Stem cells  features Self renewal  Multilineage differentiation Controlled division rate Niche dependent  Cancer stem cell features  Self renewal  Multilineage differentiation  Tumorigenic potential  Uncontrolled/ Unlimited cell division rate Niche independent (often) High invasiveness capability Drug resistance  Metastatic potential Genomic instability Existence of different pulls in one tumor Evolution The cancer stem cell theory suggests that tumors grow like normal tissues of the body, with stem cells at the starting point of an organized system that produces new cells to make a tissue grow. According to this idea, tumors contain: Cancer stem cells that divide and feed tumour growth. These cells can self-renew (copy themselves) extensively, and also produce more mature cells called transit amplifying cells.  Transit amplifying cells that divide a certain number of times then differentiate (or 'mature') into specialized tumor cells. Specialized tumor cells that do not divide and so do not contribute to tumor growth. According to this idea, the cells in a tumor are in a strictly organized system with cancer stem cells at the top of the tree, giving rise to all other cancer cells.  The stochastic model of cancer growth gives a different possible explanation of tumour growth. This theory argues that all cancer cells have the same potential to grow and divide, but each cell chooses at random between self-renewal and differentiation. The cells in a tumor are not in an organized system – any cell has the same intrinsic potential to contribute to tumor growth. p53 P38/MK2 Alternative strategies for cancer treatment Chemotherapeutic drugs as a DNA damaging agents P53 is necessary for DNA repair at G1 P53 is mutated in 50% of all cancers   Nitrogen mustards Nitrosoureas: Alkyl sulfonates Triazines temozolomide  Ethylenimines http://biochemistri.es/post/83760238677 Current and potential future research directions 1. We aimed to evaluate the resistance development of CSC to chemotherapeutic drugs  a. CRCSC are grown in elevating concentrations of 5FU until they develop the  resistance   Resistance can be developed trough a wide spectrum of protective mechanisms  including DNA damage repair, altered cell-cycle checkpoint control, malfunction of  apoptosis, drug transporters, and detoxifying enzymes       b. Genomic approach using RNA sequencing of the cells that developed resistance  to evaluate the potential mechanism of the resistance development in CRCSC  2. Using P38/MK2 cascade blockers in P53 mutants.  Thank you 

Cancer stem cells in colorectal cancer

http://nur.nu.edu.kz/bitstream/handle/123456789/321/Cancer%20stem%20cells%20in%20colorectal%20cancer.pdf?sequence=1&isAllowed=y

Cancer stem cells in colorectal cancer

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