Abstract 416: Carbon monoxide targets Notch1 and MAPK-ERK1/2 signaling pathways to block growth of lung carcinoma
| Autor: | János Fillinger, Zsuzsanna Németh, Eva Csizmadia, David A. Gallo, Balazs Dome, Alborz Feizi, Leo E. Otterbein, Mailin Li, Lisa Vikstrom, Barbara Wegiel, Daniel B. Costa, Kavita Bisht |
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| Rok vydání: | 2015 |
| Předmět: | |
| Zdroj: | Cancer Research. 75:416-416 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2015-416 |
| Popis: | We have recently shown that inhalation of low, non-toxic doses of carbon monoxide (CO) is a potential therapeutic adjuvant treatment for lung cancer and prostate cancer (Cancer Research, 2013, Wegiel B et al). We found that CO doses of 100 ppm daily or twice per week were the most effective in suppressing A549 xenograft tumors growth, Ki67 expression and increased cleaved caspase-3 staining. Additionally, we found that inhibition of xenografts and KRAS-driven lung tumor growth in response to CO was associated with increased expression of M1 macrophage markers (CD86, CD197, RANTES) and decreased M2 markers (MMR) and HO-1 blockage. We demonstrated a direct interaction between HO-1 and Notch1. Further, that CO promotes Notch 1 cleavage as well as phosphorylation of ERK1/2 in the stroma cells, which are the markers of M1 polarization. Moreover, we demonstrated a significant correlation between low HO-1 expression and high p-ERK ½ expression in primary human lung cancers (n = 30 patients). In summary, we describe a mechanism by which CO affects cancer growth through regulation of macrophage polarization via Notch1 and Erk1/2 pathways. Citation Format: Zsuzsanna Nemeth, Eva Csizmadia, Lisa Vikstrom, Mailin Li, Kavita Bisht, Alborz Feizi, David Gallo, Leo Otterbein, Janos Fillinger, Balazs Dome, Daniel B. Costa, Barbara Wegiel. Carbon monoxide targets Notch1 and MAPK-ERK1/2 signaling pathways to block growth of lung carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 416. doi:10.1158/1538-7445.AM2015-416 |
| Databáze: | OpenAIRE |
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