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Mismatch repair deficiencies transforming stem cells into cancer stem cells and therapeutic implications.

Vaish M - Mol. Cancer (2007)

Bottom Line: These cells are a common phenomenon for the hematological malignancies and solid tumors.The cells when exposed to cytotoxic agents, the apoptosis lead to cell death.The understanding of the biological functions of mismatch repair in the stem cells and its malignant counterparts could help in developing an effective novel therapies leaving residual non-tumorigenic population of cells resulting in potential cancer cures.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry, University of Lucknow-226007, UP, India. minal14@yahoo.com

ABSTRACT
For the exceptional self-renewal capacity, regulated cell proliferation and differential potential to a wide variety of cell types, the stem cells must maintain the intact genome. The cells under continuous exogenous and endogenous genotoxic stress accumulate DNA errors, drive proliferative expansion and transform into cancer stem cells with a heterogeneous population of tumor cells. These cells are a common phenomenon for the hematological malignancies and solid tumors. In response to DNA damage, the complex cellular mechanisms including cell cycle arrest, transcription induction and DNA repair are activated. The cells when exposed to cytotoxic agents, the apoptosis lead to cell death. However, the absence of repair machinery makes the cells resistant to tumor sensitizing agents and result in malignant transformation. Mismatch repair gene defects are recently identified in hematopoietic malignancies, leukemia and lymphoma cell lines. This review emphasizes the importance of MMR systems in maintaining the stem cell functioning and its therapeutic implications in the eradication of cancer stem cells and differentiated tumor cells as well. The understanding of the biological functions of mismatch repair in the stem cells and its malignant counterparts could help in developing an effective novel therapies leaving residual non-tumorigenic population of cells resulting in potential cancer cures.

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Active mismatch repair system in primary tumors help in the induction of cell death after chemotherapy. Primary tumors containing heterogeneous population of tumor cells along with small % of cancer stem cells (CSCs, represented by dark gray colored oval shape undergo chemotherapy. Presence of active mismatch repair induces cellular response followed by apoptosis, which lead to cell death. However, mismatch repair deficiency makes tumor cells insensitive to drug and it relapses.
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Figure 2: Active mismatch repair system in primary tumors help in the induction of cell death after chemotherapy. Primary tumors containing heterogeneous population of tumor cells along with small % of cancer stem cells (CSCs, represented by dark gray colored oval shape undergo chemotherapy. Presence of active mismatch repair induces cellular response followed by apoptosis, which lead to cell death. However, mismatch repair deficiency makes tumor cells insensitive to drug and it relapses.

Mentions: Most of the human cancers are identified having mismatch repair deficiency that result in defect in cell cycle and altered growth as in case of hematological malignancies. The defective MMR status in a damaged cell directly contributes to the resistant phenotype against the cytotoxic effects of chemotherapeutic drugs and thus these CSCs survive chemotherapy (Fig 2). The activation of DNA MMR system would help in inhibiting the survival mechanisms by raising the sensitivity of such cells to therapeutic drugs and reduce its tumor potential by arresting their growth. Owning to mass effect, progeny cancer cells still show the symptoms in the patients and therefore, the combinational therapy for the eradication of cancer stem cells and differentiated cells would be more effective. Antitumor treatment strategies selectively targeting the subset of tumor stem cells would be of clinical significance.


Mismatch repair deficiencies transforming stem cells into cancer stem cells and therapeutic implications.

Vaish M - Mol. Cancer (2007)

Active mismatch repair system in primary tumors help in the induction of cell death after chemotherapy. Primary tumors containing heterogeneous population of tumor cells along with small % of cancer stem cells (CSCs, represented by dark gray colored oval shape undergo chemotherapy. Presence of active mismatch repair induces cellular response followed by apoptosis, which lead to cell death. However, mismatch repair deficiency makes tumor cells insensitive to drug and it relapses.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1851711&req=5

Figure 2: Active mismatch repair system in primary tumors help in the induction of cell death after chemotherapy. Primary tumors containing heterogeneous population of tumor cells along with small % of cancer stem cells (CSCs, represented by dark gray colored oval shape undergo chemotherapy. Presence of active mismatch repair induces cellular response followed by apoptosis, which lead to cell death. However, mismatch repair deficiency makes tumor cells insensitive to drug and it relapses.
Mentions: Most of the human cancers are identified having mismatch repair deficiency that result in defect in cell cycle and altered growth as in case of hematological malignancies. The defective MMR status in a damaged cell directly contributes to the resistant phenotype against the cytotoxic effects of chemotherapeutic drugs and thus these CSCs survive chemotherapy (Fig 2). The activation of DNA MMR system would help in inhibiting the survival mechanisms by raising the sensitivity of such cells to therapeutic drugs and reduce its tumor potential by arresting their growth. Owning to mass effect, progeny cancer cells still show the symptoms in the patients and therefore, the combinational therapy for the eradication of cancer stem cells and differentiated cells would be more effective. Antitumor treatment strategies selectively targeting the subset of tumor stem cells would be of clinical significance.

Bottom Line: These cells are a common phenomenon for the hematological malignancies and solid tumors.The cells when exposed to cytotoxic agents, the apoptosis lead to cell death.The understanding of the biological functions of mismatch repair in the stem cells and its malignant counterparts could help in developing an effective novel therapies leaving residual non-tumorigenic population of cells resulting in potential cancer cures.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry, University of Lucknow-226007, UP, India. minal14@yahoo.com

ABSTRACT
For the exceptional self-renewal capacity, regulated cell proliferation and differential potential to a wide variety of cell types, the stem cells must maintain the intact genome. The cells under continuous exogenous and endogenous genotoxic stress accumulate DNA errors, drive proliferative expansion and transform into cancer stem cells with a heterogeneous population of tumor cells. These cells are a common phenomenon for the hematological malignancies and solid tumors. In response to DNA damage, the complex cellular mechanisms including cell cycle arrest, transcription induction and DNA repair are activated. The cells when exposed to cytotoxic agents, the apoptosis lead to cell death. However, the absence of repair machinery makes the cells resistant to tumor sensitizing agents and result in malignant transformation. Mismatch repair gene defects are recently identified in hematopoietic malignancies, leukemia and lymphoma cell lines. This review emphasizes the importance of MMR systems in maintaining the stem cell functioning and its therapeutic implications in the eradication of cancer stem cells and differentiated tumor cells as well. The understanding of the biological functions of mismatch repair in the stem cells and its malignant counterparts could help in developing an effective novel therapies leaving residual non-tumorigenic population of cells resulting in potential cancer cures.

Show MeSH
Related in: MedlinePlus