Abstract
Esophageal cancer is the eighth most common cancer and the sixth most common cause of cancer-related deaths worldwide. Despite the research progress in understanding the disease, the mechanism underlying the metastasis is still unclear. Here, we successfully generated a highly metastatic cell subline, designated as KYSE150-LuM, derived from an esophageal squamous cell carcinoma cell line (KYSE150) by in vivo selection. To elucidate the mechanisms driving metastasis, we characterized the gene expression differences between LuM cells and parent KYSE150 cells. IL-6, IL-1β, and LCN2, previously associated with tumor growth and metastasis, were up-regulated in LuM cells. Recent studies on cancer have increasingly focused on the tumor microenvironment, from which these cytokines are released. The fact that these three cytokines (IL-6, IL-1β, LCN2) were up-regulated in LuM cells indicates that these highly metastatic cells obtained through in vivo selection will be a useful resource for further studies on elucidating the mechanisms underlying the tumor microenvironment which is associated with cytokine-related tumor growth and metastasis. Moreover, LuM cells could disseminate to the lung in shorter period of time in vivo, indicating their utility for in vivo experiments of metastasis and new therapeutic targets in a shorter period of time than currently possible.
Highlights
Esophageal cancer is the eighth most common cancer and the sixth most common cause of cancer-related deaths worldwide [1]
The fact that these three cytokines (IL-6, IL-1β, lipocalin-2/ NGAL (LCN2)) were up-regulated in LuM cells indicates that these highly metastatic cells obtained through in vivo selection will be a useful resource for further studies on elucidating the mechanisms underlying the tumor microenvironment which is associated with cytokine-related tumor growth and metastasis
We considered that detection of metastasis by in vivo selection could reflect the ability of tumor cells to survive in the circulation and grow in a distant organ
Summary
Esophageal cancer is the eighth most common cancer and the sixth most common cause of cancer-related deaths worldwide [1]. In Asia, the most common type is esophageal squamous cell carcinoma (ESCC), which has been associated with environmental factors such as chronic smoking, alcohol consumption, and infection [2, 3]. Several genes such as ADH1B, ALDH2 [4], and YAP [5] have been identified to play a role in ESCC risk and development. Despite the research progress in understanding the disease and advances in therapeutic strategies, the 5-year relative survival rate of patients with ESCC with distant metastasis remains low at only 4.3% [6]. The mechanism underlying the metastasis of esophageal cancer is still unclear
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