Mechanisms of cancer guidance and elimination by stromal cells

2015 Fiscal Year Final Research Report

• Project/Area Number: 25290042
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Akita University
• Principal Investigator: Tanaka Masamitsu 秋田大学, 医学(系)研究科(研究院), 教授 (20291396)
• Co-Investigator(Renkei-kenkyūsha): KURIYAMA SEI 秋田大学, 医学部, 准教授 (30398226) ; ITOH GO 秋田大学, 医学部, 助教 (60607563)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: がん微小環境 / がん間質細胞 / 中皮細胞 / CAF / TAM / 癌細胞死

Outline of Final Research Achievements

We identified mechanisms that cancer associated fibroblasts (CAFs) and peritoneal mesothelial cells (PMCs) have high invasion property, and they lead cancer cell invasion. CAFs secrete Asporin, which creates a novel extracellular matrix that activate invasion by gastric cancers. Phosphorylation and activation of Tks5 was required for invasion by PMC. In addition, SKAP2 is essential for macrophages to infiltrate into tumors by forming podosomes, which regulates the size and incidence of lung metastasis. Gastric cancer cells secrete Agr2 that activates CAF invasion, and is an instructive molecule for stromal fibroblasts. On the other hand, CAFs also induce cancer cell apoptosis, which produces apoptotic vesicles that activate CAFs and establish CAF-leading mode of cancer invasion. The molecules and mechanisms identified here may become useful targets for the development of drugs aimed at manipulating cancer stromal cells.

Free Research Field

腫瘍生物学