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

Abstract

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.

Hypoxia and proangiogenic proteins in human ameloblastoma

“…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 .…”

“…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] .…”

Weiqi Decoction Attenuated Chronic Atrophic Gastritis with Precancerous Lesion through Regulating Microcirculation Disturbance and HIF-1α Signaling Pathway

“…An imbalance between cell proliferation and cell death would result in tumor formation and growth [41]. And, hypoxia is a common characteristic in tumor microenvironment and could induce the upregulation of HIF-1 α , which induces angiogenesis and also activates many other target genes mediating cell proliferation and apoptosis of cancer [42–44].…”

“…And, hypoxia is a common characteristic in tumor microenvironment and could induce the upregulation of HIF-1 α , which induces angiogenesis and also activates many other target genes mediating cell proliferation and apoptosis of cancer [42–44]. Cleaved caspase 3 is considered as an apoptosis marker and Ki 67 is considered as a proliferative cell marker in tumor formation [41, 45, 46]. Ki67 could be highly induced under hypoxia [46].…”

A Systematic Review of the Mechanisms Underlying Treatment of Gastric Precancerous Lesions by Traditional Chinese Medicine

“…Across in vitro and in vivo experiments, Xu et al [42] found that Xiao Tan He Wei decoction can inhibit cell proliferation and induce apoptosis of GPL cells by intervening in the NF-κB pathway. Caspase-3 and Ki67 are considered apoptosis and proliferative cell markers in tumor formation, respectively [82,83]. A recent study showed that the Weiqi decoction introduced above could enhance the protein expression of cleaved caspase-3 and decrease the protein expression of Ki67 in pyloric gastric mucosa in GPL rats, indicating that this decoction could regulate the imbalance of proliferation and apoptosis [39].…”