Role of hypoxia‐related proteins in invasion of ameloblastoma cells: crosstalk between <scp>NOTCH</scp>1, hypoxia‐inducible factor 1α, a disintegrin and metalloproteinase 12, and heparin‐binding epidermal growth factor

Costa, Natacha Malu Miranda da; Fialho, Amanda Dalla Vechia; Proietti, Carolina Carmine; Kataoka, Maria Sueli da Silva; Jaeger, Ruy Gastaldoni; Alves-Júnior, Sérgio Melo; Pinheiro, João de Jesus Viana

doi:10.1111/his.12922

Cited by 21 publications

(19 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, odontogenic cysts showed the highest immunoexpression of HIF-, suggesting that these lesions undergo to restricted oxygen supply. Ameloblastoma samples also showed increased expression of HIFin solid areas of epithelial islands, supporting the idea of localized intratumoral hypoxia [24].…”

Section: Discussionsupporting

confidence: 60%

See 1 more Smart Citation

Role of HIF-1α and CASPASE-3 in cystogenesis of odontogenic cysts and tumors

et al. 2017

Self Cite

View full text Add to dashboard Cite

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 Objectives: Odontogenic cysts and tumors are the most relevant lesions that affect the gnathic bones. These lesions have in common the formation of cystic areas and this common feature may suggest involvement of similar mechanisms. The hypoxia inducible factor 1 alpha (HIFa responsive protein to hypoxia and caspase-3, an irreversible apoptosis marker, may contribute to cyst formation. Thus, this study aimed to investigate the immunoexpression of these proteins in odontogenic cysts and tumors. Material and methods: Twenty cases of ameloblastoma, keratocystic odontogenic tumor (KOT) (n=20), radicular cyst (RC) (n=18), dentigerous cyst (DC) (n=11), calcifying cystic odontogenic tumor (n=8) and dental follicle (DF) (n=10) were used to investigate HIF-and caspase-3 expression in sequential serial cuts by immunohistochemistry. Results: HIF-was overexpressed in RC, DC and ameloblastoma when compared with DF. The basal and sometimes the lower suprabasal layer showed no or very low expression in DC, KOT and ameloblastoma, the last also showing strong expression in solid epithelial areas and initial cystic formation regions. Caspase-3 was found to be overexpressed in all lesions, with the highest expression in odontogenic cysts compared to tumors. HIF-and caspase-3 were localized in similar areas of the same lesions, especially in the epithelium surrounding cystic formations. Conclusions: This study showed distinct immunoexpression of HIF-and caspase-3 in odontogenic cyst and tumors, with higher expression observed in odontogenic cysts. Clinical relevance: These finding suggesting a possible correlation between hypoxia, apoptosis and cystogenesis, leading to understand the mechanisms responsible to cystic formation in odontogenic lesions.

show abstract

Section: Discussionsupporting

confidence: 60%

“…Proliferation of the epithelium and apoptosis are fundamental events in cystogenesis [12,22] and have been related to the development of odontogenic cysts and tumors [15,23]. Hypoxia has already been associated with cyst formation in ameloblastoma [24].…”

Section: Introductionmentioning

confidence: 99%

Role of HIF-1α and CASPASE-3 in cystogenesis of odontogenic cysts and tumors

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…To our knowledge, this is the first report that clearly links HB-EGF-EGFR signaling to the angiogenic switch of the MGUS-to-MM transition. So far, enhancement of HB-EGF expression in carcinogenesis has only been found in solid tumors under hypoxic conditions [29][30][31][32]. As shown in ameloblastoma, transcription and post-transcription factors such as hypoxia-inducible factor 1α (HIF-1α), ADAM-12, and NOTCH1 are directly involved in an HB-EGF autocrine amplification loop and facilitate local tumor invasiveness [29].…”

Section: Discussionmentioning

confidence: 99%

HB-EGF–EGFR Signaling in Bone Marrow Endothelial Cells Mediates Angiogenesis Associated with Multiple Myeloma

Rao

Giannico

Leone

et al. 2020

Cancers

View full text Add to dashboard Cite

Epidermal growth factor receptor (EGFR) and its ligand heparin-binding EGF-like growth factor (HB-EGF) sustain endothelial cell proliferation and angiogenesis in solid tumors, but little is known about the role of HB-EGF–EGFR signaling in bone marrow angiogenesis and multiple myeloma (MM) progression. We found that bone marrow endothelial cells from patients with MM express high levels of EGFR and HB-EGF, compared with cells from patients with monoclonal gammopathy of undetermined significance, and that overexpressed HB-EGF stimulates EGFR expression in an autocrine loop. We also found that levels of EGFR and HB-EGF parallel MM plasma cell number, and that HB-EGF is a potent inducer of angiogenesis in vitro and in vivo. Moreover, blockade of HB-EGF–EGFR signaling, by an anti-HB-EGF neutralizing antibody or the EGFR inhibitor erlotinib, limited the angiogenic potential of bone marrow endothelial cells and hampered tumor growth in an MM xenograft mouse model. These results identify HB-EGF–EGFR signaling as a potential target of anti-angiogenic therapy, and encourage the clinical investigation of EGFR inhibitors in combination with conventional cytotoxic drugs as a new therapeutic strategy for MM.

show abstract

“…Its activation plays an essential role in the invasive process, being fundamental for tumour growth and aggressiveness, with overexpression observed in many human tumours 4 , 36 – 38 . Immunohistochemistry studies have observed the overexpression of HIF-1α in AME and have discovered that this is associated with its aggressive biological behaviour 17 – 19 .…”

Section: Discussionmentioning

confidence: 99%

“…Some of these proteins have already been studied in AME, COC and DF. Three studies verified the expression of HIF-1 α and found a higher expression of this protein in AME when compared to COC and DF, and suggested that may be associated with its aggressive biological behaviour [17][18][19] . Three studies have verified the expression of VEGF and found a higher expression of this protein in AME when compared to odontogenic keratocyst, dentigerous cyst or tooth germ, suggesting that the up-regulation of this protein in AME might be associated with neoplastic or malignant changes of odontogenic epithelial cells [20][21][22] .…”

mentioning

confidence: 89%

Hypoxia and proangiogenic proteins in human ameloblastoma

Mendonça

Balbinot

Martins

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

Ameloblastomas are epithelial odontogenic tumours that, although benign, are locally invasive and may exhibit aggressive behaviour. In the tumour microenvironment, the concentration of oxygen is reduced, which leads to intratumoral hypoxia. Under hypoxia, the crosstalk between the HIF-1α, MMP-2, VEGF, and VEGFR-2 proteins has been associated with hypoxia-induced angiogenesis, leading to tumour progression and increased invasiveness. This work showcases 24 ameloblastoma cases, 10 calcifying odontogenic cysts, and 9 dental follicles, used to investigate the expression of these proteins by immunohistochemistry. The anti-HIF-1α, anti-MMP-2, anti-VEGF, and anti-VEGFR-2 primary antibodies are used in this work. The results have been expressed by the mean grey value after immunostaining in images acquired with an objective of 40×. The ameloblastoma samples showed higher immunoexpression of HIF-1α, MMP-2, VEGF, and VEGFR-2 when compared to the dental follicles and calcifying odontogenic cysts. Ameloblastomas show a higher degree of expression of proteins associated with intratumoral hypoxia and proangiogenic proteins, which indicates the possible role of these proteins in the biological behaviour of this tumour.

show abstract

Role of hypoxia‐related proteins in invasion of ameloblastoma cells: crosstalk between NOTCH1, hypoxia‐inducible factor 1α, a disintegrin and metalloproteinase 12, and heparin‐binding epidermal growth factor

Abstract: AME showed an increased presence of proteins associated with tumour invasiveness, which indicates a possible role of these proteins in the biological behaviour of this tumour.

Cited by 21 publications

References 42 publications

Role of HIF-1α and CASPASE-3 in cystogenesis of odontogenic cysts and tumors

Role of HIF-1α and CASPASE-3 in cystogenesis of odontogenic cysts and tumors

HB-EGF–EGFR Signaling in Bone Marrow Endothelial Cells Mediates Angiogenesis Associated with Multiple Myeloma

Hypoxia and proangiogenic proteins in human ameloblastoma

Contact Info

Product

Resources

About