Pilot Investigation on p75ICD Expression in Laryngeal Squamous Cell Carcinoma

Abstract

We investigated the p75 Neurotrophin Receptor (p75NTR) expression and cleavage product p75NTR Intracellular Domain (p75ICD) as potential oncogenic and metastatic markers in human Laryngeal Squamous Cell Carcinoma (LSCC). p75NTR is highly expressed in Cancer Stem Cells (CSCs) of the laryngeal epithelia and it has been proposed as a marker for stemness, cell migration, and chemo-resistance in different squamous carcinomas. To investigate the clinical significance of p75NTR cleavage products in solid tumors, full-length and cleaved p75NTR expression was analyzed in laryngeal primary tumors from different-stage LSCC patients, diagnosed at the Policlinico Umberto I Hospital. Molecular and histological techniques were used to detect the expressions of p75NTR and p75ICD, and ATP Binding Cassette Subfamily G Member 2 (ABCG2), a CSC marker. We found regulated p75NTR cleavage during squamous epithelial tumor progression and tissue invasion. Our preliminary investigation suggests p75ICD expression and localization as possible features of tumorigenesis and metastaticity. Its co-localization with ABCG2 in squamous cells in the parenchyma invaded by the tumor formation allows us to hypothesize p75NTR and p75ICD roles in tumor invasion and CSC spreading in LSCC patients. These data might represent a starting point for a comprehensive analysis of p75NTR cleavage and of its clinical relevance as a potential molecular LSCC signature, possibly helping diagnosis, and improving prognosis and personalized therapy.

Nuclear Epidermal Growth Factor Receptor Overexpression as a Survival Predictor in Oral Squamous Cell Carcinoma

“…A detailed analysis of the sublocalization of ABCG2 immunoreactivity has not been described, although several papers mention the possible importance of intracellular localization of the protein. Several studies have observed membranous and nuclear expression of ABCG2 in malignant tumor cells, such as lung and laryngeal carcinomas and glioblastoma multiforme [ 67 , 68 , 69 ]. A possible novel role of ABCG2 within the nucleus as a transcriptional regulator involved in modulation of metastasis has been proposed in lung cancer [ 68 ].…”

Significance of nuclear EGFR and ABCG2 expression in malignant transformation of oral potentially malignant disorders

“…In several papers plasma membrane, as well as nuclear ABCG2 immunoreactivity was observed in cancer cells, namely lung cancer cells, laryngeal squamous cancer cells and glioblastoma multiforme cells. [39][40][41] A potential novel role for nuclear ABCG2 was proposed, as a transcription regulator participating in modulation of cancer metastasis in lung cancer cells. 40 In our specimen beside membrane and cytoplasm ABCG2 immunoreactivity we have also observed nuclear one (Figure 1D).…”

“…In addition, detail analysis of ABCG2 sublocalization immunoreactivity was not described, although a few investigations have been reported. In several papers plasma membrane, as well as nuclear ABCG2 immunoreactivity was observed in cancer cells, namely lung cancer cells, laryngeal squamous cancer cells and glioblastoma multiforme cells 39–41 . A potential novel role for nuclear ABCG2 was proposed, as a transcription regulator participating in modulation of cancer metastasis in lung cancer cells 40 …”