Abstract 4665: Induction of receptor tyrosine kinase signaling by sera from patients with lung adenocarcinoma

Autor: Gabriela C. Lobato, Wen-Rong Lie, Selina Sayidine, Cristina Fhied, Sanjib Basu, Michael J. Liptay, Nicholas Lund, Vineela Chukkapalli, Jeffrey A. Borgia, Imad Tarhoni, Philip Bonomi, Jared Fialkoff
Rok vydání: 2017
Předmět:
Zdroj: Cancer Research. 77:4665-4665
ISSN: 1538-7445
0008-5472
DOI: 10.1158/1538-7445.am2017-4665
Popis: Background: The objective of this study was to evaluate disease stage-associated differences in receptor tyrosine kinase (RTK) signaling in A549 cells using pretreatment sera from cases of pathologically-confirmed lung adenocarcinoma or control cases derived from a lung cancer screening study. This was accomplished as a means to explore the hypothesis that circulating concentrations of decoy receptors and/or ligands, as well as disease-specific ligand degradation all regulate RTK signaling in vivo. Methods: Pretreatment peripheral blood were prepared from either from non-cancer control patients (n=30) or those with lung adenocarcinoma, consisting of stage I (T1-2N0M0, n=25); locoregionally progressed (T1-2N1-2M0, n=36) or disseminated, stage IV disease (n=43). All patients were enrolled with written informed consent to our IRB-approved, institutional biorepository. Confluent cultures of A549 cells were stimulated for 10 minutes with patient sera diluted 1:1 in RPMI-1640 followed by immediate whole cell lysate preparation. After protein determinations by BCA, 8.5 µg of each sample was interrogated using the Human RTK (phosphoprotein) kit from MilliporeSigma according to manufacturer’s instructions. After being normalized to the kit-supplied (stimulated) HeLa cell lysates, all resulting data were evaluated by one-way ANOVA (LSD and Tukey post-hoc) for categorical comparisons. Results: The most commonly observed differences in RTK signaling was noted upon comparing cohorts with locoregional (T1-2N1-2M0) progression and disseminated (stage IV) disease. Levels of in c-Met and insulin receptor (IR) signaling were higher in patients with stage IV disease relative to those with locoregional disease by 24% and 10%, respectively (both p Conclusions: We observed an apparent discoupling of certain circulating ligands in patient sera to stimulate their respective RTKs in a disease stage-specific manner. We are currently evaluating levels of circulating ligands, potential disease stage-associated (partial) proteolytic degradation, and decoy receptors to help explain these observations. Citation Format: Gabriela C. Lobato, Jared D. Fialkoff, Imad Tarhoni, Nicholas Lund, Vineela Chukkapalli, Selina Sayidine, Cristina L. Fhied, Sanjib Basu, Wen-Rong Lie, Michael J. Liptay, Philip Bonomi, Jeffrey A. Borgia. Induction of receptor tyrosine kinase signaling by sera from patients with lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4665. doi:10.1158/1538-7445.AM2017-4665
Databáze: OpenAIRE
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