BACKGROUND: Overexpression of the Hedgehog (HH) signalling pathway has been described in several malignancies and is associated with a poor prognosis. HH signalling blockade reduces tumour growth in vitro and in vivo. We aimed to determine whether head and neck squamous cell carcinomas (HNSCCs) express HH proteins in comparison to healthy mucosa. PATIENTS AND METHODS: Formalin-fixed and paraffin-embedded tissue sections of 10 patients with HNSCC were stained with fluorescence-labelled antibodies for cytokeratin and HH proteins (SHH, PTCH1/2, SMO, Gli1-3) and photographs were taken with a laser scanning microscope. The pixel count and colour intensity were analysed in RGB (red/green/blue) colour mode, and expression levels were compared to healthy mucosa. RESULTS: Image analysis in RGB mode provided objective evidence for the over-expression of HH signalling components in HNSCC, particularly with regard to the transcription factors Gli1 (10-fold) and SHH (5-fold) in comparison with healthy mucosa. The lowest levels were found for Gli3 in HNSCC. CONCLUSIONS: We postulate pivotal roles of Gli1 and SHH expression in the carcinogenesis of HNSCC. HH pathway overexpression appears to be involved in the initiation of tumour growth and spread due to its stem cell-modulating properties. Detection of HH pathway components, and especially Gli1 and SHH, in HNSCC might offer a promising target for further anticancer research in HNSCC.
BACKGROUND: Overexpression of the Hedgehog (HH) signalling pathway has been described in several malignancies and is associated with a poor prognosis. HH signalling blockade reduces tumour growth in vitro and in vivo. We aimed to determine whether head and neck squamous cell carcinomas (HNSCCs) express HH proteins in comparison to healthy mucosa. PATIENTS AND METHODS: Formalin-fixed and paraffin-embedded tissue sections of 10 patients with HNSCC were stained with fluorescence-labelled antibodies for cytokeratin and HH proteins (SHH, PTCH1/2, SMO, Gli1-3) and photographs were taken with a laser scanning microscope. The pixel count and colour intensity were analysed in RGB (red/green/blue) colour mode, and expression levels were compared to healthy mucosa. RESULTS: Image analysis in RGB mode provided objective evidence for the over-expression of HH signalling components in HNSCC, particularly with regard to the transcription factors Gli1 (10-fold) and SHH (5-fold) in comparison with healthy mucosa. The lowest levels were found for Gli3 in HNSCC. CONCLUSIONS: We postulate pivotal roles of Gli1 and SHH expression in the carcinogenesis of HNSCC. HH pathway overexpression appears to be involved in the initiation of tumour growth and spread due to its stem cell-modulating properties. Detection of HH pathway components, and especially Gli1 and SHH, in HNSCC might offer a promising target for further anticancer research in HNSCC.
Authors: Anjali P Patni; M K Harishankar; Joel P Joseph; Bhuvanadas Sreeshma; Rama Jayaraj; Arikketh Devi Journal: Cell Oncol (Dordr) Date: 2021-03-11 Impact factor: 6.730
Authors: Elana J Fertig; Ana Markovic; Ludmila V Danilova; Daria A Gaykalova; Leslie Cope; Christine H Chung; Michael F Ochs; Joseph A Califano Journal: PLoS One Date: 2013-11-04 Impact factor: 3.240
Authors: Abu Shadat M Noman; Rashed R Parag; Muhammad I Rashid; Mohammad Z Rahman; Ali A Chowdhury; Afrin Sultana; Chandsultana Jerin; Ayesha Siddiqua; Lutfur Rahman; Afsana Shirin; Junayed Nayeem; Reaz Mahmud; Sonam Akther; Rajib K Shil; Ikram Hossain; Sharmin Alam; Arfina Chowdhury; Shabnam B Basher; Abul Hasan; Shammy Bithy; Jannatul Aklima; Mizanur Rahman; Nabila Chowdhury; Tahmina Banu; Bedri Karakas; Herman Yeger; Walid A Farhat; Syed S Islam Journal: Ther Adv Med Oncol Date: 2020-03-13 Impact factor: 8.168