Oral Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

Mass Spectrometry Imaging of RTKi with protein target in human lung cancer tumor xenograft mouse (#229)

Tae young Kim 1 , Yonghyo Kim 2 , Yutaka Sugihara 2 , Melinda Rezeli 2 , Marcell Szasz 3 , Gy├Ârgy Marko-Varga 2 , HoJeong Kwon 1
  1. Yonsei university, Yonsei-ro Seodaemungu, SEOUL, South Korea
  2. Lund University, Lund
  3. National Koranyi Institute, Budapest

Receptor tyrosine kinase inhibitor (RTKi) has been widely used to treat NSCLC (non-small-cell lung carcinoma) patients. Currently, RTKi has been known to acquire resistance in the patients treated leading to low efficacy. Many studies have aimed to unveil the cause of resistance by exploring the molecular mechanism in vitro. However, low efficacy of RTKi in tumor growth in vivo have not been fully addressed so far. Here, we propose the novel evidence of RTKi's low efficacy through analysis of its distribution image using MALDI MSI (matrix-assisted laser desorption ionization imaging) and IHC (Immunohistochemistry) of a protein target of RTKi. We found that H1299, human lung cancer cells, show weak growth inhibition upon RTKi treatment leading to low efficacy in H1299 tumor xenograft model mouse. From the model mouse, we identified that RTKi was distributed on RTKi-treated tumor, liver and kidney tissue co-localizing with its target protein. Additionally, RTKi localized higher in liver and kidney than tumor tissue from the analysis of quantification analysis. Collectively, these results demonstrated that low efficacy of RTKi in H1299 tumor xenograft model comes in part from its nonspecific distribution in a number of organs.