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Macrophages and endothelial cells orchestrate tumor-associated angiogenesis in oral cancer via hedgehog pathway activation.
Tumour Biol 2016; 37(7):9233-41TB

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, in addition to the participation of both SHH and IHH ligands. Endothelial cells were also found to exhibit positivity with respect to Hh pathway components and we surmise that these molecules may play a role in tumor angiogenesis. CD163+ macrophages were also observed to express IHH, a ligand of this pathway, in addition to being associated with tumor neovascularization.

Authors+Show Affiliations

Laboratory of Pathology and Molecular Biology, Oswaldo Cruz Foundation, Gonçalo Moniz Research Center, R. Waldemar Falcão, 121, Candeal, Salvador, Bahia, CEP: 40296-710, Brazil.Laboratory of Experimental Pathology, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil.Laboratory of Pathology and Molecular Biology, Oswaldo Cruz Foundation, Gonçalo Moniz Research Center, R. Waldemar Falcão, 121, Candeal, Salvador, Bahia, CEP: 40296-710, Brazil.Laboratory of Pathology and Molecular Biology, Oswaldo Cruz Foundation, Gonçalo Moniz Research Center, R. Waldemar Falcão, 121, Candeal, Salvador, Bahia, CEP: 40296-710, Brazil.Laboratory of Pathology and Molecular Biology, Oswaldo Cruz Foundation, Gonçalo Moniz Research Center, R. Waldemar Falcão, 121, Candeal, Salvador, Bahia, CEP: 40296-710, Brazil.Laboratory of Oral Surgical Pathology, School of Dentistry of the Federal University of Bahia, Salvador, Bahia, Brazil.Laboratory of Pathology and Molecular Biology, Oswaldo Cruz Foundation, Gonçalo Moniz Research Center, R. Waldemar Falcão, 121, Candeal, Salvador, Bahia, CEP: 40296-710, Brazil. gurgel.clarissa@gmail.com. Laboratory of Oral Surgical Pathology, School of Dentistry of the Federal University of Bahia, Salvador, Bahia, Brazil. gurgel.clarissa@gmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26768620

Citation

Valverde, Ludmila de Faro, et al. "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, vol. 37, no. 7, 2016, pp. 9233-41.
Valverde Lde F, Pereira Tde A, Dias RB, et al. Macrophages and endothelial cells orchestrate tumor-associated angiogenesis in oral cancer via hedgehog pathway activation. Tumour Biol. 2016;37(7):9233-41.
Valverde, L. d. e. . F., Pereira, T. d. e. . A., Dias, R. B., Guimarães, V. S., Ramos, E. A., Santos, J. N., & Gurgel Rocha, C. A. (2016). 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, 37(7), pp. 9233-41. doi:10.1007/s13277-015-4763-6.
Valverde Lde F, et al. Macrophages and Endothelial Cells Orchestrate Tumor-associated Angiogenesis in Oral Cancer Via Hedgehog Pathway Activation. Tumour Biol. 2016;37(7):9233-41. PubMed PMID: 26768620.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Macrophages and endothelial cells orchestrate tumor-associated angiogenesis in oral cancer via hedgehog pathway activation. AU - Valverde,Ludmila de Faro, AU - Pereira,Thiago de Almeida, AU - Dias,Rosane Borges, AU - Guimarães,Vanessa Sousa Nazaré, AU - Ramos,Eduardo Antônio Gonçalves, AU - Santos,Jean Nunes, AU - Gurgel Rocha,Clarissa Araújo, Y1 - 2016/01/15/ PY - 2015/11/02/received PY - 2015/12/29/accepted PY - 2016/1/16/entrez PY - 2016/1/16/pubmed PY - 2017/2/7/medline KW - Hedgehog proteins KW - Immunohistochemistry KW - Oral cancer KW - Squamous cell carcinoma SP - 9233 EP - 41 JF - Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine JO - Tumour Biol. VL - 37 IS - 7 N2 - 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, in addition to the participation of both SHH and IHH ligands. Endothelial cells were also found to exhibit positivity with respect to Hh pathway components and we surmise that these molecules may play a role in tumor angiogenesis. CD163+ macrophages were also observed to express IHH, a ligand of this pathway, in addition to being associated with tumor neovascularization. SN - 1423-0380 UR - https://www.unboundmedicine.com/medline/citation/26768620/Macrophages_and_endothelial_cells_orchestrate_tumor_associated_angiogenesis_in_oral_cancer_via_hedgehog_pathway_activation_ L2 - https://link.springer.com/article/10.1007/s13277-015-4763-6 DB - PRIME DP - Unbound Medicine ER -