J Cancer 2015; 6(12):1236-1244. doi:10.7150/jca.12626

Research Paper

A Fraction of CD133+ CNE2 Cells Is Made of Giant Cancer Cells with Morphological Evidence of Asymmetric Mitosis

Qingping Jiang1,2#, Qianbing Zhang2#, Shuang Wang2, Siming Xie2, Weiyi Fang2, Zhen Liu1,2, Jinsong Liu3✉, Kaitai Yao2✉

1. Department of Pathology, Key Laboratory of Major Obstetrics Diseases of Guangdong Province, the Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
2. Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
3. Department of Pathology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
# These authors contributed equally to this work.

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Jiang Q, Zhang Q, Wang S, Xie S, Fang W, Liu Z, Liu J, Yao K. A Fraction of CD133+ CNE2 Cells Is Made of Giant Cancer Cells with Morphological Evidence of Asymmetric Mitosis. J Cancer 2015; 6(12):1236-1244. doi:10.7150/jca.12626. Available from http://www.jcancer.org/v06p1236.htm

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CD133 has been suggested as a broad-spectrum marker for cancer stem cells(CSCs). The present study investigated the expression of CD133 in biopsy tissues of nasopharyngeal carcinoma (NPC), NPC cell lines and the immortalized cell line NP69 by immunohistochemistry, flow cytometry and qRT-PCR. CD133+ cancer cells were isolated using magnetic-activated cell sorting technology. The study demonstrated that CD133+ cells are rare in NPC tissues and cell lines and that their self-renewal and proliferation abilities are stronger than those of CD133- cells and suggested that CD133+ NPC cells have characteristics of cancer stem cells. We further observed CD133+ cancer cells using a light microscope and scanning electron microscope. Generally, CD133+ cells are small, regular and round with small microvilli. On the other hand, CD133- cells are more polymorphic and larger with long micromicrovilli. Additionally, in some fields, several giant cancer cells (GCCs) in the CD133+ cell group were identified under the light microscope. Most of them were polynuclear cells. Under the scanning electron microscope, we found indefinite regular small bodies on the surface of or surrounding the giant cancer cells, some of which appeared to be creeping out the parental cells. This phenomenon was not observed in the CD133- cell groups. Through comparison with descriptions of apoptotic bodies in the literature and from the results of the acridine orange test, we propose that some of the small bodies are daughter cells of the GCCs. This phenomenon is a mode of division of cancer cells called neosis, or budding, which is a form of reproduction for simple organisms. Budding is satisfied with the rapid speed of tumor development. GCCs could be isolated by CD133 beads because the daughter cells have stem-cell characteristics and express stem-cell markers.

Keywords: CD133, stem cell, giant cancer cells, budding, nasopharyngeal carcinoma