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Eukaryotic cell encystation and cancer cell dormancy: is a greater devil veiled in the details of a lesser evil?

Baig AM, Khan NA, Abbas F - Cancer Biol Med (2015)

Bottom Line: These dormant cells veil themselves from detection by imaging and/or using biomarkers, which imposes an additional problem in targeting such cells.A similar form of hibernation process known as encystation is studied in detail for pathogenic unicellular eukaryotic microorganisms.We propose a strategy to induce dormancy and exit this state by application of knowledge gained from the encystation induction and retrieval processes in pathogenic eukaryotic microorganisms.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological and Biomedical Sciences, Aga Khan University, Karachi 75300, Pakistan.

ABSTRACT
Cancer cell dormancy is the main cause of cancer recurrence and failure of therapy as dormant cells evade not only the anticancer drugs but also the host immune system. These dormant cells veil themselves from detection by imaging and/or using biomarkers, which imposes an additional problem in targeting such cells. A similar form of hibernation process known as encystation is studied in detail for pathogenic unicellular eukaryotic microorganisms. By examination using microarray gene expression profiles, immunocytochemistry tools, and siRNAs during the process of encystation, understanding the covert features of cancer cell dormancy as proposed could be possible. This knowledge can be extended to dormant cancer cells to uncover the mechanisms that underlie this ghost, yet dangerous state of human cancers. We propose a strategy to induce dormancy and exit this state by application of knowledge gained from the encystation induction and retrieval processes in pathogenic eukaryotic microorganisms. Given that early detection and characterization of dormant malignant tumor cells is important as a general strategy to monitor and prevent the development of overt metastatic disease, this homology may enable the design of therapies that could either awake the dormant cell from dormancy to make it available for therapies or prolong such a phase to make cancer appear as a chronic disease.

No MeSH data available.


Related in: MedlinePlus

(A) Cyst of Acanthamoeba castellanii exhibiting double-walled structure; (B) Induced cancer stem cells in lung carcinoma. During maturation of these cells, mitochondria appeared to play a key role in wall development, as these organelles assumed a centripetal layout helping to delimit border.
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f1: (A) Cyst of Acanthamoeba castellanii exhibiting double-walled structure; (B) Induced cancer stem cells in lung carcinoma. During maturation of these cells, mitochondria appeared to play a key role in wall development, as these organelles assumed a centripetal layout helping to delimit border.

Mentions: In this letter, we bring to debate the thought whether the process of encystation can provide insights into hibernating cancer cells. Cancer cell dormancy and its subsequent recurrence to active form are a daunting threat to our fight against cancer. Determining the epigenetic and metabolic characteristics of these dormant cells would be a significant success in oncotherapy. Given that cancer dormant cells exhibit low metabolic profile and altered epigenetic regulation of gene expression, targeting such ghost cells has become problematic. To date, no specific genetic signature has been identified that could explain the molecular mechanisms associated with tumor dormancy. However, several studies proposed the existence of genetic and molecular pathways that might govern dormancy and escape from dormancy1. As evolutionary biology uses unicellular eukaryotic microorganisms to understand the complex mechanisms of multicellular organisms, we hypothesize that studying encystation characteristics in the ancestral “MOTHER” eukaryotic cells, such as primitive eukaryotic pathogenic amoebas, could possibly broaden our understanding of the complexities of cancer cell dormancy. Given that both phenotypes (encystation and dormancy) present a “state of hibernation” (Figure 1), the conceptual resemblance is remarkable, but molecular similarities may also exist. We need to determine and examine the stimuli for encystation and dormancy, downstream pathways, effects on organelles, changes in the cell membranes, and metabolic pathways to test this hypothesis. Based on the findings, we can possibly compute the conserved “MOTHER” features in these eukaryotic cell models. Further, examination by using microarray gene expression profiles, immunocytochemistry tools, and siRNAs, we are able to understand the covert features of cancer cell dormancy.


Eukaryotic cell encystation and cancer cell dormancy: is a greater devil veiled in the details of a lesser evil?

Baig AM, Khan NA, Abbas F - Cancer Biol Med (2015)

(A) Cyst of Acanthamoeba castellanii exhibiting double-walled structure; (B) Induced cancer stem cells in lung carcinoma. During maturation of these cells, mitochondria appeared to play a key role in wall development, as these organelles assumed a centripetal layout helping to delimit border.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383842&req=5

f1: (A) Cyst of Acanthamoeba castellanii exhibiting double-walled structure; (B) Induced cancer stem cells in lung carcinoma. During maturation of these cells, mitochondria appeared to play a key role in wall development, as these organelles assumed a centripetal layout helping to delimit border.
Mentions: In this letter, we bring to debate the thought whether the process of encystation can provide insights into hibernating cancer cells. Cancer cell dormancy and its subsequent recurrence to active form are a daunting threat to our fight against cancer. Determining the epigenetic and metabolic characteristics of these dormant cells would be a significant success in oncotherapy. Given that cancer dormant cells exhibit low metabolic profile and altered epigenetic regulation of gene expression, targeting such ghost cells has become problematic. To date, no specific genetic signature has been identified that could explain the molecular mechanisms associated with tumor dormancy. However, several studies proposed the existence of genetic and molecular pathways that might govern dormancy and escape from dormancy1. As evolutionary biology uses unicellular eukaryotic microorganisms to understand the complex mechanisms of multicellular organisms, we hypothesize that studying encystation characteristics in the ancestral “MOTHER” eukaryotic cells, such as primitive eukaryotic pathogenic amoebas, could possibly broaden our understanding of the complexities of cancer cell dormancy. Given that both phenotypes (encystation and dormancy) present a “state of hibernation” (Figure 1), the conceptual resemblance is remarkable, but molecular similarities may also exist. We need to determine and examine the stimuli for encystation and dormancy, downstream pathways, effects on organelles, changes in the cell membranes, and metabolic pathways to test this hypothesis. Based on the findings, we can possibly compute the conserved “MOTHER” features in these eukaryotic cell models. Further, examination by using microarray gene expression profiles, immunocytochemistry tools, and siRNAs, we are able to understand the covert features of cancer cell dormancy.

Bottom Line: These dormant cells veil themselves from detection by imaging and/or using biomarkers, which imposes an additional problem in targeting such cells.A similar form of hibernation process known as encystation is studied in detail for pathogenic unicellular eukaryotic microorganisms.We propose a strategy to induce dormancy and exit this state by application of knowledge gained from the encystation induction and retrieval processes in pathogenic eukaryotic microorganisms.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological and Biomedical Sciences, Aga Khan University, Karachi 75300, Pakistan.

ABSTRACT
Cancer cell dormancy is the main cause of cancer recurrence and failure of therapy as dormant cells evade not only the anticancer drugs but also the host immune system. These dormant cells veil themselves from detection by imaging and/or using biomarkers, which imposes an additional problem in targeting such cells. A similar form of hibernation process known as encystation is studied in detail for pathogenic unicellular eukaryotic microorganisms. By examination using microarray gene expression profiles, immunocytochemistry tools, and siRNAs during the process of encystation, understanding the covert features of cancer cell dormancy as proposed could be possible. This knowledge can be extended to dormant cancer cells to uncover the mechanisms that underlie this ghost, yet dangerous state of human cancers. We propose a strategy to induce dormancy and exit this state by application of knowledge gained from the encystation induction and retrieval processes in pathogenic eukaryotic microorganisms. Given that early detection and characterization of dormant malignant tumor cells is important as a general strategy to monitor and prevent the development of overt metastatic disease, this homology may enable the design of therapies that could either awake the dormant cell from dormancy to make it available for therapies or prolong such a phase to make cancer appear as a chronic disease.

No MeSH data available.


Related in: MedlinePlus