Hydrogen Sulfide and Hydrogen Sulfide-Synthesizing Enzymes Are Altered in a Case of Oral Adenoid Cystic Carcinoma

Abstract

Adenoid cystic carcinomas (ACC) constitute 1% of all head and neck malignancies and are very rare in the oral cavity. With < 60 oral ACCs described, their pathobiology is incompletely understood. Here, we report a case of oral cavity ACC in a 54-year-old woman. Since recent studies have demonstrated that several human tumors overexpress the hydrogen sulfide (H₂S)-synthesizing enzymes cystathionine-β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST), and also show dysregulated H₂S levels, we examined these biomarkers in the oral ACC and compared the results to those of adjacent benign oral epithelium. Western blotting was used to compare the protein expression of CBS, CSE, 3-MST, nicotinamide phosphoribosyl transferase, and mitoNEET in ACC and adjacent benign oral mucosae. High-performance liquid chromatography was used to quantify the differences in tissue H₂S concentrations between the two biopsy types. We found that all the proteins examined here were increased in the ACC compared to adjacent benign oral mucosae. Interestingly, H₂S concentrations were decreased approximately 30% in ACC compared to benign mucosae. Thus, in one example of this rare tumor type, the enzymes that synthesize H₂S are increased, while tissue H₂S levels are lower than those found in adjacent benign oral mucosae. Although limited to a single rare tumor type, to our knowledge this is the second time H₂S concentrations have been directly quantified inside a human tumor. Last, our results may indicate that alterations in H₂S synthesis and metabolism may be important in the pathobiology of ACC.

Role of 3-Mercaptopyruvate Sulfurtransferase in the Regulation of Proliferation, Migration, and Bioenergetics in Murine Colon Cancer Cells

“…3-MST expression was also clearly demonstrated in many different primary tumor tissues, including human brain gliomas [33], human melanoma specimens [34], human colon cancer resections [26], human lung carcinoma resections [27], human urothelial cell carcinoma of the bladder resections [30,31], human oral squamous cell carcinoma resections [35], and oral adenoid cystic carcinoma resections [36]. In many (but not all) of these studies, the expression of 3-MST tended to increase with higher grades of the malignancy.…”

Potential role of the 3-mercaptopyruvate sulfurtransferase (3-MST)—hydrogen sulfide (H2S) pathway in cancer cells

“…In contrast, in human melanoma specimens, the expression of 3-MST was detectable with some frequency (25-50% of the sections analyzed) and it was undetectable in the other portion (50-75% of the sections) [57]. In human colon cancer resections [51], in human lung carcinoma resections [52], in human urothelial cell carcinoma of the bladder resections [55,56] in human oral squamous cell carcinoma resections [61] and in oral adenoid cystic carcinoma resections [62] 3-MST expression has been demonstrated by immunohistochemistry and/or by Western blotting; in all of these cancers tumor 3-MST expression was either significantly higher or tended to be higher than 3-MST expression in the surrounding noncancerous tissues. In contrast, in human papillary thyroid cancer resections 3-MST expression was moderate and was not different from the surrounding tissue [63], while in renal cell carcinoma resections the level of 3-MST expression was highly variable [54].…”

Emerging roles of cystathionine β-synthase in various forms of cancer

“…In human melanoma specimens, the expression of 3-MST was detectable in 25–50% of the sections analyzed [ 216 ]. 3-MST was also detected in human colon cancer resections [ 49 ], in human lung carcinoma resections, human bladder urothelial cell carcinoma resections, human oral squamous cell carcinoma resections and in oral adenoid cystic carcinoma resections [ 49 , 67 , 69 , 75 , 237 ]; in some instances its levels were significantly higher or tended to be higher than its levels in the surrounding normal tissues. Paired analysis of colon cancer specimen 3-MST expression suggests that there may be a subgroup of colon cancer patients where colon cancer 3-MST levels are substantially higher than surrounding tissue 3-MST [ 49 ], but this possibility remains to be further assessed in larger datasets.…”