Macrophages (MΦs) and reactive oxygen species (ROS) are implicated in carcinogenesis. The oxidative stress sensor, transient receptor potential ankyrin 1 (TRPA1), activated by ROS, ap-pears to contribute to lung and breast cancer progression. Although TRPA1 expression has been reported in melanoma cell lines, and oxidative stress has been associated with melanocytic trans-formation, their role in melanoma remains poorly known. Here, we localized MΦs, the final end-product of oxidative stress, 4-hydroxynonenal (4-HNE), and TRPA1 in tissue samples of human common dermal melanocytic nevi, dysplastic nevi, and thin (pT1) and thick (pT4) cutaneous mela-nomas. The number (amount) of intratumoral and peritumoral M2 MΦs and 4-HNE staining pro-gressively increased with tumor severity, while TRPA1 expression was similar in all samples. Hy-drogen peroxide (H2O2) evoked a TRPA1-dependent calcium response in two distinct melanoma cell lines (SK-MEL-28 and WM266-4). Furthermore, H2O2 induced a TRPA1-dependent H2O2 release that was prevented by the TRPA1 antagonist, A967079, or Trpa1 gene silencing (siRNA). ROS release from infiltrating M2 MΦs may target TRPA1-expressing melanoma cells to amplify the oxidative stress signal that affects tumor cell survival and proliferation.
The trpa1 channel amplifies the oxidative stress signal in melanoma / De Logu F.; de Araujo D.S.M.; Ugolini F.; Iannone L.F.; Vannucchi M.; Portelli F.; Landini L.; Titiz M.; De Giorgi V.; Geppetti P.; Massi D.; Nassini R.. - In: CELLS. - ISSN 2073-4409. - ELETTRONICO. - 10:(2021), pp. 0-0. [10.3390/cells10113131]
The trpa1 channel amplifies the oxidative stress signal in melanoma
De Logu F.;Ugolini F.;Iannone L. F.;Vannucchi M.;Portelli F.;Landini L.;Titiz M.;De Giorgi V.;Geppetti P.;Massi D.;Nassini R.
2021
Abstract
Macrophages (MΦs) and reactive oxygen species (ROS) are implicated in carcinogenesis. The oxidative stress sensor, transient receptor potential ankyrin 1 (TRPA1), activated by ROS, ap-pears to contribute to lung and breast cancer progression. Although TRPA1 expression has been reported in melanoma cell lines, and oxidative stress has been associated with melanocytic trans-formation, their role in melanoma remains poorly known. Here, we localized MΦs, the final end-product of oxidative stress, 4-hydroxynonenal (4-HNE), and TRPA1 in tissue samples of human common dermal melanocytic nevi, dysplastic nevi, and thin (pT1) and thick (pT4) cutaneous mela-nomas. The number (amount) of intratumoral and peritumoral M2 MΦs and 4-HNE staining pro-gressively increased with tumor severity, while TRPA1 expression was similar in all samples. Hy-drogen peroxide (H2O2) evoked a TRPA1-dependent calcium response in two distinct melanoma cell lines (SK-MEL-28 and WM266-4). Furthermore, H2O2 induced a TRPA1-dependent H2O2 release that was prevented by the TRPA1 antagonist, A967079, or Trpa1 gene silencing (siRNA). ROS release from infiltrating M2 MΦs may target TRPA1-expressing melanoma cells to amplify the oxidative stress signal that affects tumor cell survival and proliferation.
I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
