Deciphering biological characteristics of tumorigenic subpopulations in human colorectal cancer reveals cellular plasticity

解读人类结直肠癌致瘤亚群的生物学特征揭示细胞可塑性

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作者:Hamed Mirzaei, Hossein Salehi, Amirhossein Sahebkar, Amir Avan, Mahmoud Reza Jaafari, Afshin Namdar, Abbas Rezaei, Hamid Reza Mirzaei

Background

It is supposed that human colorectal cancer consists of a phenotypically distinct population of tumorigenic cancer cells known as cancer stem cells (CSCs) which play a pivotal role in cancer progression, maintenance, metastasis, and the relapse. The

Conclusion

We also conclude that this cellular plasticity is greatly affected by tumor microenvironment cues and the role of CSCs niche in cancer therapeutic strategies should be precisely considered.

Methods

Using our optimized protocols, unfixed colorectal tumors were enzymatically and mechanically dissociated into single cells followed by evaluation of postdigestion viability. The obtained single cell suspensions were then subjected to cell sorting using magnetic beads according to CD133 marker. The resultant CD133+ and CD133- cell subsets were cultured in specific cell culture medium followed by aldehyde dehydrogenases (ALDH) activity assessment and flow cytometric analyses.

Results

The results demonstrate that CD133+ cells have smaller size and lower complexity of intracellular structure, sphere formation ability, and ALDH enzyme activity while CD133- cells isolated from primary colon cancer samples were not able to form a sphere and did not show ALDH enzyme activity. Intriguingly, CD133- cells isolated from metastatic colorectal cancer specimen were able to form a sphere and shown ALDH enzyme activity. The present study indicates that our results are in agreement with SC theory and possibility of the existence of cellular plasticity among cancer subpopulations should be portrayed.

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