Esophageal squamous cell carcinoma (ESCC) is responsible for about 90% of esophageal cancers, particularly in East Asia. Recent research published in The American Journal of Pathology suggests that periostin, also known as POSTN, plays a role in advancing ESCC by increasing the migration of cancer and stromal cells in cancer-associated fibroblasts (CAFs). As a result, it could potentially be a new target for treating ESCC.and the role of cancer-associated fibroblasts (CAFs) in this process, researchers focused on the protein called S100A4. They found that S100A4 plays a crucial role in promoting cancer cell migration and stromal cell migration in CAFs. This discovery suggests that S100A4 could be a promising target for new therapeutic approaches to treat ESCC.
Dr. Yu-ichiro Koma, who led the study at Kobe University Graduate School of Medicine, emphasized the importance of understanding the role of CAFs in the tumor microenvironment and their contribution to the progression of ESCC. He highlighted the need for further research to uncover the underlying mechanisms of esophageal cancer development and progression.
In order to gain a better understanding of ESCC progression and the involvement of CAFs, the research team focused on the protein S100A4. Their findings revealed that S100A4 plays a crucial role in promoting cancer cell migration and stromal cell migration in CAFs. As a result, S100A4 could potentially serve as a novel therapeutic target for treating ESCC.
Investigators utilized CAFs to create CAF-like cells by directly co-culturing human bone marrow-derived MSCs with ESCC cells. This led to an increase in periostin expression. The introduction of recombinant human periostin activated the Akt and Erk signaling pathways in ESCC cells, ultimately boosting their survival and migration. Furthermore, periostin also enhanced the migration of MSCs and macrophages, imparting TAM-like characteristics to the macrophages. Immunohistochemistry revealed the clinical importance of periostin and its correlation with high expression levels.The study found a strong association between tumor invasiveness, vessel invasion, advanced pathological stage, CAF marker expression, and TAM infiltration. When ESCC cells were directly cocultured with these factors, they exhibited increased malignancy characteristics, such as enhanced tumor survival, growth, and migration, as well as heightened phosphorylation of Akt and Erk.
Dr. Koma stated that periostin, which is up-regulated in CAFs upon direct contact with cancer cells, plays a significant role in promoting ESCC progression and the migration of stromal cells like CAFs and TAMs. Periostin also boosts the migration of mesenchymal stem cells and macrophages, while also giving macrophages tumor-associated macrophage-like properties.CAF-secreted periostin was found to be a factor in the development of the tumor microenvironment. Dr. Koma’s study established a direct coculture system between ESCC cells and MSCs, which led to the promotion of the malignant phenotype of ESCC cells. Patients with high periostin expression in ESCC showed poorer postoperative outcomes, suggesting that periostin could be a potential therapeutic target for treating this type of esophageal cancer and could also serve as a prognostic indicator. Esophageal cancer is the seventh most common cancer globally and the sixth leading cause of cancer-related death, with ESCC being the most common histological subtype.The two main types of esophageal cancer are ESCC and esophageal adenocarcinoma, with ESCC making up about 90% of cases, particularly in East Asia. In East Asia and East Africa, esophageal cancer is among the top five causes of cancer deaths, and the five-year survival rate for ESCC is around 20%, which is not good. The likelihood of metastasis is high, even if the tumor is superficial, leading to a poor prognosis. Early esophageal cancer often doesn’t show symptoms, so it is usually diagnosed at an advanced stage.
