Abstract B031: Effect of macrophage inflammatory response and VHL mutation status on the development of clear cell renal carcinoma

Abstract

Kidney[A1] cancer is a serious health care issue problem around the worldworldwide. It is symptomless asymptomatic in the early stage and is refractory to most [A2] of the cancer treatment modalities. The most prevalent form of the kidney cancer, renal cell carcinoma of the clear-cell type (ccRCC), is mainly caused by loss-of-function of the von Hippel-Lindau tumor suppressor gene (VHL). VHL protein is an E3 ubiquitin ligase and. iIts most prominentmain degradation target is the alpha subunit of the hypoxia-inducible factor (HIF). However, the etiology of ccRCC formation development remains unclear. Recent animal model studies in our laboratory have indicatedWe recently observed that tissue inflammation and fibrosis are the early events in ccRCC development is tissue inflammation and fibrosis. This interesting result provides important supports for the concept notion that chronic inflammation is can induce tumorigenesisic and. It is also consistent with the epidemiological evidence linking inflammatory kidney disease and kidney cancer. In the current present study, we explored the mechanistic detailsm by which changes within the VHL mutant cells orchestrateeffect[A3] a systemic inflammatory response[A4], and found that the metabolic abnormalities caused by VHL gene mutation lead to unresolved chronic endoplasmic reticular stress (ER stress), which in turn induces activation of JNK and NFκB, two major components of pro-inflammatory signaling pathways components[A5]. On the other hand, our previous study also demonstrated that LCN2[A6] sensitizes the inflammatory response of VHL mutant HK-2 cells in vhl mutant condition and the chemotactic abilityies of macrophage RAW 264.7 cells. [A7] However, the wider implication of this tumorigenic process [A8] that of RAW 264.7 cells is stillremains unclear and then warrants further investigationswill be discussed. Accumulating evidence indicated that Lon protease (Lon) is a multifunctional protein that mediatesinvolved in protein quality control and oxidative stress responses in mitochondria. However, the molecular mechanisms underlying the effects of Lon on the progression of ccRCC progression and inflammatory response inof the vhl VHL mutant condition cells remain largely unknown. Therefore, in this study, we aimed to elucidate the inflammatory effect role of inflammatory RAW 264.7 macrophages on the development of ccRCC development inusing cultured vhl VHL mutant renal tubular cells and RAW264.7 cells. Moreover, d Decoding how the action involved signaling pathways drive or suppress signals cellular and inflammatory responses or preventing it is a major research challenge. Once elucidated, it will for future research and will require the definition ofprovide the rationale for drug design and application on anti-ccRCC formation therapeutic strategies based onvia targeting macrophages infiltration.

Citation Format: Chan-Yen Kuo. Effect of macrophage inflammatory response and VHL mutation status on the development of clear cell renal carcinoma [abstract]. In: Proceedings of the AACR Special Conference: Advances in Kidney Cancer Research; 2023 Jun 24-27; Austin, Texas. Philadelphia (PA): AACR; Cancer Res 2023;83(16 Suppl):Abstract nr B031.