Glypican-1, -3, -5 (GPC1, GPC3, GPC5) and Hedgehog Pathway Expression in Oral Squamous Cell Carcinoma.

Autor: Schlaepfer Sales CB; Federal University of Bahia., Guimarães VSN; Federal University of Bahia.; Oswaldo Cruz Foundation, Gonçalo Moniz Institute, Laboratory of Pathology and Molecular Biology, Salvador, Brazil., Valverde LF; Federal University of Bahia.; Oswaldo Cruz Foundation, Gonçalo Moniz Institute, Laboratory of Pathology and Molecular Biology, Salvador, Brazil., Dias RB; Federal University of Bahia.; Oswaldo Cruz Foundation, Gonçalo Moniz Institute, Laboratory of Pathology and Molecular Biology, Salvador, Brazil., Freitas RD; Federal University of Bahia.; Oswaldo Cruz Foundation, Gonçalo Moniz Institute, Laboratory of Pathology and Molecular Biology, Salvador, Brazil., Siquara da Rocha LO; Oswaldo Cruz Foundation, Gonçalo Moniz Institute, Laboratory of Pathology and Molecular Biology, Salvador, Brazil., Coelho de Miranda M; Federal University of Bahia., Vilas Bôas DS; Federal University of Bahia., Gonçalves Agra IM; Federal University of Bahia., Dos Santos JN; Federal University of Bahia., Gurgel Rocha CA; Federal University of Bahia.; Oswaldo Cruz Foundation, Gonçalo Moniz Institute, Laboratory of Pathology and Molecular Biology, Salvador, Brazil.
Jazyk: angličtina
Zdroj: Applied immunohistochemistry & molecular morphology : AIMM [Appl Immunohistochem Mol Morphol] 2021 May-Jun 01; Vol. 29 (5), pp. 345-351.
DOI: 10.1097/PAI.0000000000000907
Abstrakt: Proteoglycans are involved in tumor development and may regulate the Hedgehog (HH) pathway. This study aimed to investigate the gene and protein expression of glypican-1 (GPC1), -3 (GPC3), and -5 (GPC5) in oral squamous cell carcinoma (OSCC) and tumor-free lateral margins (TM) and their association with the HH pathway. Quantitative PCR was performed for GPC1, GPC3, GPC5, SHH, PTCH1, SMO, and GLI1 genes in samples of OSCC (n=31), TM (n=12), and non-neoplastic oral mucosa (NNM) of healthy patients (n=6), alongside an immunohistochemical evaluation of GPC1, GPC3, and GPC5 proteins and HH proteins SHH and glioma-associated oncogene homolog 1 (GLI1). Double staining for GPC3/SHH, GPC5/SHH, GPC3/tubulin [ac Lys40], GPC5/Tubulin [ac Lys40], and GPC5/GLI1 was also performed. Overexpression of GPC1 and GPC5 in tumor samples and underexpressed levels of GPC3 gene transcripts were observed when compared with TM (standard sample). HH pathway mRNA aberrant expression in OSCC samples and a negative correlation between GPC1 and GPC5 at transcription levels were detected. GPC1 staining was rare in OSCC, but positive cells were found in NNM and TM. Otherwise positive immunostaining for GPC3 and GPC5 was observed in OSCCs, but not in NNM and TM. Blood vessels adjacent to tumor islands were positive for GPC1 and GPC5. Co-localization of GPC3-positive and GPC5-positive cells with SHH and Tubulin [ac Lys40] proteins was noted, as well as of GPC5 and GLI1. The absence of the GPC1 protein in neoplastic cells, underexpression of the GPC3 gene, and co-localization of GPCs and HH proteins may indicate the maintenance of aberrant HH pathway activation in OSCC.
Competing Interests: The authors declare no conflict of interest.
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Databáze: MEDLINE