Angiogenic effects of GRP78 in exosomes derived from cancer cells

[Abstract]
We are studying the cancer progression mechanism caused by a protein called GRP78 secreted by cancer cells, focusing on the exosome, an extracellular transport vesicle.

[Background]
In normal cells, GRP78 works inside the endoplasmic reticulum to maintain cell function. However, when cells become cancerous, they also exist outside the endoplasmic reticulum, and work on all cell functions to promote cancer progression. In addition, it is becoming clear that GRP78 secreted from cancer cells affects other normal cells and is involved in the construction of the tumor microenvironment (TME). (See figure)
“Tumor microenvironment construction” is a sophisticated tumor growth strategy in which cancer cells work on surrounding non-cancer cells to change their properties. The remodeling of cell properties by this mechanism changes the environment surrounding the tumor, the “tumor microenvironment”, to be suitable for cancer progression and is the source of tumor growth and metastasis.

[Our research]
Our purpose is to clarify the cancer progression effect of GRP78 in exosomes which secreted by cancer cells. We are doing joint research with Dr. Lin from E-SHOU University (Taiwan), who specializes in research on gastric cancer.
The amount of GRP78 secreted by cells using exosomes is very small, and it is very difficult to measure the exact amount. Therefore, in this research, the ultra-sensitive measurement technology of protein called “Thio-NAD cycling ELISA method” possessed by Ito Laboratory is used to enable the quantitative study of extracellular GRP78. This is the breakthrough research of exosome.

[Results and prospects]
In previous studies, we measured the abundance of GRP78 in exosomes secreted by multiple types of cultured cancer cells and clarified that the abundance varies between cancer cell types. This difference may be related to the different character of each cancer cell. In that case, we can explore the specific mechanism of cancer progression.
We also measure GRP78 in exosomes in the serum of cancer patients, and we want to clarify the cancer progression effect of GRP78 in vivo.