Posted: Thursday, May 26, 2022
A study conducted by Kashif Rasheed, PhD, of the University of Tromsø, Norway, and colleagues uncovered a possible role of Merkel cell polyomavirus tumor (T) antigens and interleukin-33 (IL-33) in Merkel cell carcinoma. By comparing human cytokine and receptor transcript levels in virus-positive and virus-negative cell lines, the investigators found that this virus’s large and small T antigens appear to be linked to an altered expression of IL-33 and its receptors, ST2/IL-1RL1 and IL-1RAcP. The investigators’ findings were published in the International Journal of Molecular Sciences.
“The expression of IL-33 and its receptor ST2/IL-1RL1 may constitute an autocrine or paracrine survival loop, which contributes to the growth and survival of Merkel cell carcinoma,” suggested the study authors. “Therapeutic strategies for targeting IL-33/ST2 signaling for the treatment of various inflammatory diseases are evolving. However, additional studies are required to establish that blocking the IL-33/ST2 axis may have therapeutic potential for [cancer] treatment.”
Tumor tissues and clinical data were obtained from 168 patients diagnosed with Merkel cell carcinoma in Finland between 1979 and 2013. Recombinant proteins included human full-length and cytokine-domain IL-33. IL-33 expression was induced by transfecting MCC-13 cells with Merkel cell polyomavirus large T antigens.
When compared with MCC-13 cells, the number of differentially expressed genes was 65 in the MKL-1 cell line, 71 in the MKL-2 cell line, 63 in the MS-1 cell line, and 70 in the WaGa cell line. Essentially, a total of 22 different inflammatory cytokines and receptors were differentially expressed between virus-positive and the virus-negative MCC-13 cell line. Furthermore, there appeared to be twofold to threefold higher IL-33 levels in virus-positive (MKL-1, MKL-2, MS-1, WaGa) than virus-negative (MCC-13, MCC-26, and UISO) cell lines.
“These results show that full-length and truncated large T antigens, as well as small T antigens, can increase the transcriptional activity of the IL-33 promoter and enhance IL-33 expression levels,” concluded the investigators.
Disclosure: The study authors reported no conflicts of interest.