CD44v3+/CD24− cells possess cancer stem cell-like properties in human oral squamous cell carcinoma

Abstract

Cancer stem cells (CSCs) or cancer stem cell-like cells (CSC-LCs) are a minority population of cells that relate to tumor progression, metastasis and drug resistance. To identify CSC-LCs in oral squamous cell carcinoma (OSCC), we used two OSCC cell lines, SAS and OSC20, and cell surface markers, CD44v3 and CD24. In addition, we examined CD44v3 and CD24 expression immunohistochemically and evaluated the relationship between the expression and clinicopathological parameters in 50 OSCC tissues. In SAS and OSC20, CD44v3+/CD24− cells showed a higher sphere forming ability than the other fractions, i.e., CD44v3+/CD24+, CD44v3−/CD24− and CD44v3−/CD24+ cells. The proportion of CD44v3+/CD24− cells in SAS and OSC20 was 10.7 and 24.1%, respectively. Regarding SAS, CD44v3+/CD24− cells also showed a higher drug resistance for CDDP, 5-FU and cetuximab and expressed higher mRNA levels of CSC property-related genes than the other cell fractions. The tumorigenicity of CD44v3+/CD24− cells was not significantly different from the other fractions in SAS. An immunohistochemical study revealed a significant correlation between CD44v3 expression in the invasive portion and lymph node metastasis. Kaplan Meier analysis revealed cases with CD44v3 expression in the invasive portion tended to show poor overall survival (OS) compared with those without CD44v3, and there was a significant difference in OS between CD44v3+/CD24− and CD44v3−/CD24− immunophenotypes in the invasive portion. In conclusion, the results suggest that the CD44v3+/CD24− cell population displays CSC-LC properties in a human OSCC cell line. Additionally, we present evidence that CD44v3 immunoexpression and CD44v3+/CD24− immunophenotypes could give prognostic information associated with unfavorable clinical outcomes.

CD44v3 protein-carrying tumor-derived exosomes in HNSCC patients’ plasma as potential noninvasive biomarkers of disease activity

“…[19][20][21][22] CD44v3 has been of special interest as a potential biomarker of disease progression in HNSCC, because its overexpression in HNSCC cells associates with increased proliferation, migration and a greater metastatic potential of HNSCC cancer cell lines and tumor tissues. 22,23 CD44v3 overexpression in HNSCC correlates with poor outcome, and similar associations were reported for colorectal cancer and malignant melanoma. [23][24][25] Further, increased mRNA and protein levels of CD44v3 in HNSCC tumor tissues correlated to poor overall patient CONTACT Theresa L. Whiteside whitesidetl@upmc.edu UPMC Hillman Cancer Center, 5117 Centre Avenue, Suite 1.27, Pittsburgh, PA 15213, USA Supplemental data for this article can be accessed on the publisher's website.…”

Separation of plasma-derived exosomes into CD3(+) and CD3(−) fractions allows for association of immune cell and tumour cell markers with disease activity in HNSCC patients

“…CD44v3 is a variant of CD44, which is created through alternative exon splicing . CD44v3 is over‐expressed in many HNSCC, and its expression associates with poor outcome in HNSCC . Here, we show that the CD3 (–) exosome fraction was enriched for CD44v3 (+) TEX, which represented ∼30% of the non‐captured CD3 (–) exosome fraction.…”

“…CD44v3 is a variant of CD44, which is created through alternative exon splicing [32]. CD44v3 is over-expressed in many HNSCC, and its expression associates with poor outcome in HNSCC [33,34].…”

SOX8 regulates cancer stem‐like properties and cisplatin‐induced EMT in tongue squamous cell carcinoma by acting on the Wnt/β‐catenin pathway

“…It has been reported that CD441/CD242 cells possess CSC-like features in oral squamous cell carcinoma. 19,20 Our study showed the proportion of CD44 1 CD242 cells in CAL27-res and SCC9res cells (24.5 and 26%) was higher than that in CAL27 and SCC9 cells (10.9 and 13.3%) by flow cytometric analysis (Supporting Information Fig. 3d).…”