In human HNSCC tissues, CD44 expression was upregulated and was associated with blood vessels, although no correlation between MVD and CD44 expression was found.
Using a literature survey on potential surface molecules followed by immunohistochemical validation, we identified CD44 variant 6 (CD44v6) as a constitutively expressed antigen in the invasion zone of HNSCC lesions.
CD44 was expressed on the surface of poorly differentiated tumour cells, and within the The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma samples, its messenger RNA levels were higher in tumours compared to normal.
CD44 has been identified as a potential cancer stem cell marker in head and neck squamous cell carcinoma and its overexpression in pagetoid cells represents a novel treatment target.
To examine the association between CD44 and c-MET expression in relation to p16 and EGFR in patients with head and neck squamous cell carcinoma (HNSCC).
These newly-discovered HA/CD44-mediated oncogenic signaling pathways delineate unique tumor dynamics with implications for defining the drivers of HNSCC progression processes.
CD44v6, an oncogenic variant of the cell surface molecule CD44, is a promising molecular target since it exhibits a unique expression pattern in HNSCC and is associated with drug- and radio-resistance.
Thus, the aim of this study was to evaluate the association of a novel cancer stem cell (CSC) marker, CD44 variant 9 (CD44v9), with cellular refractoriness to chemoradioselection in advanced head and neck squamous cell carcinoma (HNSCC).
As a result, VPA inhibited the self-renewal abilities of HNSCC CSCs during two serial passages and decreased the expression of stem cell markers, such as Oct4, Sox2 and CD44.
We enriched the CD44(+) CSC population, and grew them in spheroid cultures. sFRP4 decreased the proliferation and increased the sensitivity of spheroids to a commonly used drug in HNSCC, namely cisplatin.
Two CSC-like populations, CD44(high)/BMI1(high) and CD44(high)/ALDH(high), were enriched from HNSCC cell lines and evaluated for the expression of SMURF1 by qRT-PCR, flow cytometry, and immunoblotting.
To address this hypothesis, we generated xenograft HNSCC tumors with University of Michigan-squamous cell carcinoma 22B (UM-SCC-22B) cells and observed that cisplatin treatment increased (P = .0013) the fraction of CSCs [i.e., aldehyde dehydrogenase activity high and cluster of differentiation 44 high (ALDH(high)CD44(high))].
Interestingly, the expression of CD166, rather than that of the well-established HNSCC CSC marker CD44, was significantly related to the malignant behavior of HNSCC.
Further analysis reveals that microRNA-302 (miR-302) is controlled by an upstream promoter containing Oct4-Sox2-Nanog-binding sites, whereas chromatin immunoprecipitation (ChIP) assays demonstrate that stimulation of miR-302 expression by HA-CD44 is Oct4-Sox2-Nanog-dependent in HNSCC-specific CSCs.
Recent data support the role of ALDH1(+) CD44(+) CSC in HNSCC, since the implantation of a few ALDH1(+) CD44(+) cells consistently gives rise to tumors that can be serially passaged in vivo.
This novel Nanog/Stat-3 signaling pathway-specific mechanism involved in miR-21 production is significant for the formation of future intervention strategies in the treatment of HA/CD44-activated HNSCC.