p75 neurotrophin receptor: A potential surface marker of tongue squamous cell carcinoma stem cells

Abstract

The present study detected p75 neurotrophin receptor (p75NTR) expression in tongue squamous cell carcinoma (TSCC) cell lines, in order to define the biological properties of p75NTR+ cells and to confirm the use of p75NTR+ as a surface marker for TSCC stem cells. p75NTR+ cells were separated from Tca-8113 and CAL-27 TSCC cells by fluorescence-activated cell sorting. Colony formation, MTT and scratch assays, and a tumorigenicity analysis were performed to measure self-renewal and proliferation, multidirectional differentiation, and tumorigenicity of p75NTR+ cells. p75NTR+ cells comprised 3.1 and 1.9% of Tca-8113 and CAL-27 cells (mean of three experiments), respectively, and were more able to form colonies compared with non-sorted cells (P<0.01). In addition, the proportion of p75NTR+ cells generated from monoclonal p75NTR+ cells decreased to 14.5 (Tca-8113) and 5.8% (CAL-27) of cells within 2 weeks, thus suggesting that p75NTR+ cells are able to generate p75NTR+ and p75NTR− cells. Furthermore, p75NTR+ cells exhibited increased proliferation, as evidenced by MTT assay (P<0.01) and had greater metastatic ability according to the scratch assay (P<0.01), compared with non-sorted cells. p75NTR+ cells also exhibited a greater tumorigenic capacity compared with non-sorted cells. In conclusion, p75NTR+ cells isolated from TSCC cell lines possess the characteristics of cancer stem cells; therefore, p75NTR may be considered a useful surface marker for the identification of TSCC stem cells.

Pilot Investigation on p75ICD Expression in Laryngeal Squamous Cell Carcinoma

“…A deeper understanding of the opposite p75NTR and p75ICD-mediated biological functions could also help in explaining some apparently contradictory effects of p75NTR in cancers. In fact, behind the cancer-specific developmental mechanisms, p75NTR has been reported to be pro-apoptotic in gastric cancer [ 14 ] and proliferative in tongue [ 9 ] and esophageal squamous carcinogenesis [ 6 ].…”

“…For example, p75NTR has been implicated in melanoma [ 3 , 4 , 5 , 6 ], and its expression has been demonstrated in several non-neuronal cancers, such as Schwann cell tumors, ganglioneuroma, granular cell tumors, and malignant peripheral nerve sheath tumors [ 7 ]. The expression of p75NTR is also associated with increased cell proliferation in tongue squamous cell carcinoma [ 8 , 9 ], while the antibody to p75NTR results in decreased HNSCC formation in vivo [ 10 ]. Moreover, the anti-proliferative effect of p75NTR knockdown in cancer cells has been found to be mediated by the regulation of the p53 tumor suppression [ 11 ], which has been recently reported as an independent prognostic factor in HNSCC patients [ 12 ], further supporting the role of p75NTR in the progression of squamous carcinomas.…”

Precision Medicine Revolutionizing Esophageal Cancer Treatment: Surmounting Hurdles and Enhancing Therapeutic Efficacy through Targeted Drug Therapies

“…SP cells, which are enriched in CSCs, express high levels of ATP-binding cassette (ABC) transporters, such as ABCG5 and ABCG2, which are responsible for effluxing multiple drugs and conferring multidrug resistance [120]. Additionally, esophageal CSCs may hinder the drug influx process through the downregulation of Copper Uptake Protein 1 (CTR1), which is facilitated by p75 neurotrophin-receptor (p75NTR)-positive cells possessing stem-cell-like characteristics and resistance to cisplatin [121,122].In summary, esophageal CSCs utilize specific membrane transporter distributions to maintain intracellular drug concentrations at safe levels and evade the cytotoxic effects of chemotherapy.…”

Precision Medicine Revolutionizing Esophageal Cancer Treatment: Surmounting Hurdles and Enhancing Therapeutic Efficacy through Targeted Drug Therapies"

“…SP cells, which are enriched in CSCs, express high levels of ATP-binding cassette (ABC) transporters, such as ABCG5 and ABCG2, responsible for effluxing multiple drugs and conferring multidrug resistance [110]. Additionally, esophageal CSCs may hinder the drug influx process through the downregulation of Copper Uptake Protein 1 (CTR1), which is facilitated by p75 neurotrophin receptor (p75NTR) positive cells possessing stem cell-like characteristics and resistance to cisplatin [111,112].In summary, esophageal CSCs utilize specific membrane transporter distributions to maintain intracellular drug concentrations at safe levels and evade the cytotoxic effects of chemotherapy.…”