Expression of cancer stem cell marker during 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis

Abstract

One of the theories regarding oral carcinogenesis is that the tumor growth is initiated from cancer stem cells (CSCs) that self-renew and give rise to differentiated tumor cells, like stem cells do in normal tissues. The most common methods of CSC identification are based on CSC marker expression in carcinogenesis. This study examined the expression of CD133 and CD44, the most commonly used CSC biomarkers in oral squamous cell sarcoma (SCC), with the goal of identifying molecular biomarkers whose expression is associated with the multistep oral carcinogenesis. The expression of CD133, CD44, proliferating cell nuclear antigen (PCNA), and Cytokeratin (CK) was examined by Western blot analysis and confirmed by immunohistochemistry in a 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis model. Also, the expression of aldehyde dehydrogenase 1 (ALDH1), OCT-4 and Nanog were investigated for alteration of cancer cell stemness by Western blot. Along with the progress of multistep carcinogenesis, there were slight increases of CD133 and CD44 expression in the dysplasia group compared with normal rats. However, CD133 protein level was significantly overexpressed in SCC. The expression of PCNA and CK were low in normal group, but sequentially increased in SCC. ALDH1, Nanog and OCT-4 expression were significantly increased according to SCC grade during carcinogenesis. The findings indicate that CD133 is useful in identifying oral CSCs, which suggests that CD133 may serve as a predictor to identify CSCs with a high risk of oral cancer development.

Cancer Stem Cells in Squamous Cell Carcinoma

“…Also, CSCs share certain regulators with normal SCs. For example, SCC CSCs express factors that regulate self-renewal in embryonic SCs, such as SOX2, MYC, and OCT-4 (Bose and Shenoy, 2014; Boumahdi et al, 2014; Lim et al, 2014). Similarly, some common “stemness” pathways are activated in follicular SCs and CSCs, such as Wnt signaling (Malanchi et al, 2008; White et al, 2013).…”

Current Cancer Stem Cell Biomarkers in Tongue Squamous Cell Carcinoma

“…Furthermore, CD44 and CD133 expressions were found to be strongly overexpressed in 4-Nitroquinoline 1oxide induced TSCC in addition to several other cancer stem cell markers including ALDH1, Nanog and OCT-4. These findings point out the importance of CD44 as well as other cancer stem cell markers in the multistep carcinogenesis process of TSCC (Lim et al 2014).…”

“…CSCs were reported to be enriched in the highly invasive UM1 cell line which is strongly positive for CD44 expression but were not present in the less invasive UM2 cell line (Misuno et al 2013). In a recent study, where 4-Nitroquinoline 1-oxide was used to induce tongue cancer in mice, CD44 expression along with CD133 was found to be slightly overexpressed in dysplasia group compared to normal rats (Lim et al 2014). Furthermore, CD44 and CD133 expressions were found to be strongly overexpressed in 4-Nitroquinoline 1oxide induced TSCC in addition to several other cancer stem cell markers including ALDH1, Nanog and OCT-4.…”

Regulation of Osteosclerosis by Inoculated Cd133+ PC3 Cells in Bone‐marrow Microenvironmental Niches

“…Consequently, CD133 is considered an important cell surface marker for a subpopulation of cancer initiating cells (CICs) in brain tumors, colon carcinoma, head and neck cancer, hepatocellular carcinoma, thyroid carcinoma, and PC . Previously, we demonstrated that upregulation of CD133 on head and neck cancer cells and in head and neck squamous cell carcinoma tissue correlates with chemoresistance to anticancer drugs such as 5‐FU . Recent reports suggest that expression of CD133 by tumor tissues may be a prognostic indicator for tumor regrowth, malignant progression, and patient survival .…”

“…(14)(15)(16)(17) Previously, we demonstrated that upregulation of CD133 on head and neck cancer cells and in head and neck squamous cell carcinoma tissue correlates with chemoresistance to anticancer drugs such as 5-FU. (18,19) Recent reports suggest that expression of CD133 by tumor tissues may be a prognostic indicator for tumor regrowth, malignant progression, and patient survival. (20) Nevertheless, the CD133mediated molecular mechanisms that regulate differentiation of osteocytes and osteoclasts during bone metastasis of PC remain unclear.…”