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Metastatic colon cancer cell populations contain more cancer stem-like cells with a higher susceptibility to natural killer cell-mediated lysis compared with primary colon cancer cells.

Kim GR, Ha GH, Bae JH, Oh SO, Kim SH, Kang CD - Oncol Lett (2015)

Bottom Line: Consistently, an increased clonogenicity of KM12L4a and KM12SM compared with KM12C cells in soft agar was observed.Furthermore, the results indicated an increased susceptibility of KM12L4a and KM12SM to NK cell-mediated cytotoxicity in comparison with KM12C cells.These results indicated that metastatic colon cancer cell populations may consist of more cancer stem-like cells, and have greater susceptibility to NK cell-mediated lysis compared with that of primary colon cancers.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Pusan National University School of Medicine, Yangsan, Gyeongsangnam-do 626-870, Republic of Korea.

ABSTRACT

In the present study, the soft agar clonogenicity and the susceptibility of clonogenic cancer cells to natural killer (NK) cells were compared between primary colon cancer cells (KM12C) and metastatic colon cancer cells (KM12L4a and KM12SM) to determine whether the metastatic cancer cells consisted of more cancer stem-like cells and were resistant to NK cell-mediated lysis. The majority of colon cancer cells were positive for putative cancer stem cell markers, including CD44, CD133 and EpCAM, with the exception of KM12C cells, of which only ~55% were positive for CD133. In addition, the expression levels of sex determining region Y-box 2, Nanog and octamer-binding transcription factor 4, which are essential for maintaining self-renewal, were higher in KM12L4a and KM12SM compared with that in KM12C cells. Consistently, an increased clonogenicity of KM12L4a and KM12SM compared with KM12C cells in soft agar was observed. The expression levels of NKG2D ligands, including major histocompatibility complex class I polypeptide-related sequence A/B and UL16 binding protein 2, and of death receptor 5 were significantly higher in KM12L4a and KM12SM than in KM12C cells. Furthermore, the results indicated an increased susceptibility of KM12L4a and KM12SM to NK cell-mediated cytotoxicity in comparison with KM12C cells. These results indicated that metastatic colon cancer cell populations may consist of more cancer stem-like cells, and have greater susceptibility to NK cell-mediated lysis compared with that of primary colon cancers.

No MeSH data available.


Related in: MedlinePlus

Comparison of expression levels of putative colon CSC markers and stemness-related genes between the primary KM12C cells and the highly metastatic KM12L4A and KM12SM cells. Flow cytometric analysis of putative colon CSC markers was conducted in (A) KM12C, (B) KM12L4A and (C) KM12SM cells. (D) Expression of SOX-2, Nanog, and OCT-4 in three sublines. Data are presented as the mean ± standard error of three independent experiments, and were analyzed using a Student’s t-test (*P<0.05; **P<0.01). CSC, cancer stem cell; SOX-2, sex determining region Y-box 2; OCT-4, octamer-binding transcription factor 4.
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f1-ol-09-04-1641: Comparison of expression levels of putative colon CSC markers and stemness-related genes between the primary KM12C cells and the highly metastatic KM12L4A and KM12SM cells. Flow cytometric analysis of putative colon CSC markers was conducted in (A) KM12C, (B) KM12L4A and (C) KM12SM cells. (D) Expression of SOX-2, Nanog, and OCT-4 in three sublines. Data are presented as the mean ± standard error of three independent experiments, and were analyzed using a Student’s t-test (*P<0.05; **P<0.01). CSC, cancer stem cell; SOX-2, sex determining region Y-box 2; OCT-4, octamer-binding transcription factor 4.

Mentions: To examine whether highly metastatic cancer cell populations contain a greater proportion of CSCs, the surface expression of several putative colon CSC markers was determined in KM12C (Fig. 1A), KM12L4A (Fig. 1B) and KM12SM (Fig. 1C) cells. The majority of KM12L4A and KM12SM cells were positive for CD44 (96.89 and 99.19%, respectively), CD133 (91.9 and 98.29%, respectively) and EpCAM (97.39 and 98.81%, respectively). Although a high proportion of KM12C cells were also positive for CD44 and EpCAM, CD133 expression was only detected in ~55% of these cells. In addition, the mRNA levels of SOX-2, NANOG and OCT-4, which are essential for maintaining self-renewal (19), were higher in KM12L4a and KM12SM compared with that in KM12C cells (Fig. 1D). These results indicate that highly metastatic cancer cells may have more cancer stem-like cells than primary cancer cells.


Metastatic colon cancer cell populations contain more cancer stem-like cells with a higher susceptibility to natural killer cell-mediated lysis compared with primary colon cancer cells.

Kim GR, Ha GH, Bae JH, Oh SO, Kim SH, Kang CD - Oncol Lett (2015)

Comparison of expression levels of putative colon CSC markers and stemness-related genes between the primary KM12C cells and the highly metastatic KM12L4A and KM12SM cells. Flow cytometric analysis of putative colon CSC markers was conducted in (A) KM12C, (B) KM12L4A and (C) KM12SM cells. (D) Expression of SOX-2, Nanog, and OCT-4 in three sublines. Data are presented as the mean ± standard error of three independent experiments, and were analyzed using a Student’s t-test (*P<0.05; **P<0.01). CSC, cancer stem cell; SOX-2, sex determining region Y-box 2; OCT-4, octamer-binding transcription factor 4.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4356422&req=5

f1-ol-09-04-1641: Comparison of expression levels of putative colon CSC markers and stemness-related genes between the primary KM12C cells and the highly metastatic KM12L4A and KM12SM cells. Flow cytometric analysis of putative colon CSC markers was conducted in (A) KM12C, (B) KM12L4A and (C) KM12SM cells. (D) Expression of SOX-2, Nanog, and OCT-4 in three sublines. Data are presented as the mean ± standard error of three independent experiments, and were analyzed using a Student’s t-test (*P<0.05; **P<0.01). CSC, cancer stem cell; SOX-2, sex determining region Y-box 2; OCT-4, octamer-binding transcription factor 4.
Mentions: To examine whether highly metastatic cancer cell populations contain a greater proportion of CSCs, the surface expression of several putative colon CSC markers was determined in KM12C (Fig. 1A), KM12L4A (Fig. 1B) and KM12SM (Fig. 1C) cells. The majority of KM12L4A and KM12SM cells were positive for CD44 (96.89 and 99.19%, respectively), CD133 (91.9 and 98.29%, respectively) and EpCAM (97.39 and 98.81%, respectively). Although a high proportion of KM12C cells were also positive for CD44 and EpCAM, CD133 expression was only detected in ~55% of these cells. In addition, the mRNA levels of SOX-2, NANOG and OCT-4, which are essential for maintaining self-renewal (19), were higher in KM12L4a and KM12SM compared with that in KM12C cells (Fig. 1D). These results indicate that highly metastatic cancer cells may have more cancer stem-like cells than primary cancer cells.

Bottom Line: Consistently, an increased clonogenicity of KM12L4a and KM12SM compared with KM12C cells in soft agar was observed.Furthermore, the results indicated an increased susceptibility of KM12L4a and KM12SM to NK cell-mediated cytotoxicity in comparison with KM12C cells.These results indicated that metastatic colon cancer cell populations may consist of more cancer stem-like cells, and have greater susceptibility to NK cell-mediated lysis compared with that of primary colon cancers.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Pusan National University School of Medicine, Yangsan, Gyeongsangnam-do 626-870, Republic of Korea.

ABSTRACT

In the present study, the soft agar clonogenicity and the susceptibility of clonogenic cancer cells to natural killer (NK) cells were compared between primary colon cancer cells (KM12C) and metastatic colon cancer cells (KM12L4a and KM12SM) to determine whether the metastatic cancer cells consisted of more cancer stem-like cells and were resistant to NK cell-mediated lysis. The majority of colon cancer cells were positive for putative cancer stem cell markers, including CD44, CD133 and EpCAM, with the exception of KM12C cells, of which only ~55% were positive for CD133. In addition, the expression levels of sex determining region Y-box 2, Nanog and octamer-binding transcription factor 4, which are essential for maintaining self-renewal, were higher in KM12L4a and KM12SM compared with that in KM12C cells. Consistently, an increased clonogenicity of KM12L4a and KM12SM compared with KM12C cells in soft agar was observed. The expression levels of NKG2D ligands, including major histocompatibility complex class I polypeptide-related sequence A/B and UL16 binding protein 2, and of death receptor 5 were significantly higher in KM12L4a and KM12SM than in KM12C cells. Furthermore, the results indicated an increased susceptibility of KM12L4a and KM12SM to NK cell-mediated cytotoxicity in comparison with KM12C cells. These results indicated that metastatic colon cancer cell populations may consist of more cancer stem-like cells, and have greater susceptibility to NK cell-mediated lysis compared with that of primary colon cancers.

No MeSH data available.


Related in: MedlinePlus