M. Kang

Fibroblast-associated tumour microenvironment induces vascular structure-networked tumouroid

In vitro three-dimensional (3D) tumour models mimic natural cancer tissue in vivo, bridging the gap between conventional 2D in vitro testing and animal models. Stromal and cancer tissues with extracellular matrix (ECM) can provide a tumour microenvironment (TME) with cell-to-cell and cell-to-ECM interactions. These interactions induce the exchange of biophysical factors, contributing to the progression, metastasis, and drug resistance of cancer. Here, we describe a 3D in vitro lung cancer model cultured in a microfluidic channel that is able to confirm the role and function of various stromal cells in tumourigenesis, thereby representing an in vivo-like TME. We founded that biophysical factors contribute to the role of fibroblast cells in tumour formation, especially, producing a nascent vessel-like tubular structure, resulting in the formation of vascularized tumour tissue. Fibroblast cells altered the gene expression of the cancer cells to enhance metastasis, survival, and angiogenesis. The device could be used for developing and screening anti-cancer drugs through the formation of the same multicellular tumour spheroids under TME interactions. We believe this microfluidic system provides interaction of TME for cancer research by culturing stromal tissue.

Verteporfin inhibits gastric cancer cell growth by suppressing adhesion molecule FAT1

Gastric cancer (GC) is a leading cause of death worldwide and in urgent need of targeted drug development. In the current, we investigated the ability of a repositioned drug verteporfin (VP), originally a treatment for macular degeneration, to inhibit GC cell growth. VP inhibited growth of various GC cell lines. Gene expression profiling of GC cell lines treated with VP revealed that migration-related genes and those with oncogenic potential were down-regulated. Of these genes, we found that FAT1, an adhesion molecule promoting cell invasion, was highly suppressed by VP. Silencing of FAT1 suppressed cell migration and invasion as VP did. FAT1 expression was up-regulated in tumors, and patients with high FAT1-expressing tumors had a worse prognosis. We propose that VP- targeting FAT1 to suppress metastatic potential is a promising therapeutic strategy against GC.

Abstract 1808: Nuclear receptor, ESRRG functions as tumor suppressor by preventing Helicobacter pylori infection in gastric cancer

Gastric cancer (GC) is the most common cancer type in Asia. Surgical resection and chemotherapy is standard treatment of GC. Molecular therapeutic targets and mechanism contributing to develop the gastric cancer is poorly understood. To discover the molecular target in gastric cancer, we analyzed gene expression data from gastric cancer patients. Data analysis reveals that nuclear receptor ESRRG is top candidate gene conferring the tumor suppressive property in gastric cancer. ESRRG expression is down-modulated by Helicobacter pylori (H. pylori) infection, which is one of causing factor triggering gastric cancer. In addition, ectopically over-expressed ESRRG protects the cell from H. pylori infection and suppressed cancer cell growth in vitro and in vivo mouse model. Gene expression profile reveals that TFF1, which is well known as tumor suppressor in gastric cancer is down-stream target of ESRRG and ESRRG well reflects clinical outcome in gastric cancer. Our study provides new molecular insights how ESRRG regulates gastric cancer cell growth induced by H. pylori and suggests possibility that ESSRRG can be therapeutic target for the treatment of gastric cancer patients. Citation Format: Myoung-Hee Kang, Yong-Soo Lee, Jin-Hak Jung, Young Soo Park, Jin-Yong Jeong, Mi-Na Kweon, Chan-Ki Paik, Seung-Jae Myung, Yun-Yong Park. Nuclear receptor, ESRRG functions as tumor suppressor by preventing Helicobacter pylori infection in gastric cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1808.