Macrophages and endothelial cells orchestrate tumor-associated angiogenesis in oral cancer via hedgehog pathway activation

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
Ludmila de Faro ValverdeClarissa Araújo Gurgel Rocha

Abstract

The present study aimed to evaluate the role of Hedgehog (Hh) molecule expression in association with the clinical aspects of oral squamous cell carcinoma (OSCC), as well as angiogenesis and CD163+ macrophages. Twenty-eight cases of OSCC, nine cases of tumor-free resection margins (TM), and four cases of non-neoplastic oral mucosa (NNM) were submitted to immunohistochemistry to detect proteins Sonic Hedgehog (SHH), Indian Hedgehog (IHH), GLI1, CD163, and CD105. Protein colocalization with respect to SHH/CD163, IHH/CD163, GLI1/CD163, and GLI1/CD105 was assessed by immunohistochemical double staining. In tumor parenchyma, SHH and IHH were present in the cytoplasm of neoplastic cells, while GLI1 was observed in cytoplasm and nucleus. Endothelial cells were found to express SHH, IHH, and GLI1 within CD105+ vessels, and a positive correlation between infiltrating macrophage density (IMD) and microvascular density (MVD) was observed in cases of OSCC and TM. When compared to TM and NNM, the OSCC cases demonstrated higher immunoreactivity for SHH (p = 0.01), IHH (p = 0.39), GLI1 (p = 0.03), IMD (p = 0.0002), and MVD (p = 0.0002). Our results suggest the participation of the Hh pathway in OSCC by way of autocrine and paracrine signaling...Continue Reading

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Citations

Sep 10, 2020·International Journal of Molecular Sciences·Jéssica Mariane Ferreira MendesClarissa Araújo Gurgel Rocha
Jun 27, 2019·International Journal of Molecular Sciences·Candice ChapoulyMarie-Ange Renault
Jun 6, 2020·Frontiers in Oncology·Xiaowei ChenXiaobing Shen
Oct 2, 2020·Journal of Molecular Histology·Vanessa Sousa Nazare GuimaraesClarissa Araújo Gurgel Rocha
Dec 4, 2020·International Journal of Molecular Sciences·Nathan Moreau, Yves Boucher
Apr 6, 2021·Frontiers in Oncology·Eleni Marina KalogirouPanagiotis F Christopoulos
Jan 30, 2021·Applied Immunohistochemistry & Molecular Morphology : AIMM·Caroline B Schlaepfer SalesClarissa A Gurgel Rocha

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