S100A11 contributes to tumor progression with cross talking between muscle invasive bladder cancer cells and fibroblasts

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18561
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Okayama University
• Principal Investigator: Mitsui Yosuke 岡山大学, 大学病院, 医員 (60803781)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 膀胱がん / 癌関連線維芽細胞 / S100たんぱく質 / RAGE

Outline of Final Research Achievements

Muscle invasive bladder cancer (MIBC) shows a highly aggressive features leading to poor survival. It has been shown that extracellular S100A11 provides cancer cells with increased ability for survival or mobility through receptor for advanced glycation endproducts (RAGE) in an autocrine manner. However, the role of the extracellular S100A11 in MIBC progression remains unclear. In the present study, we investigated the extracellular role of S100A11 in cross-talking between MIBC cells and surrounding fibroblasts in MIBC progression. An abundant S100A11 secreted from bladder cancer cells stimulated neighboring fibroblasts through receptor for RAGE upon S100A11 binding, and was followed by　an enhanced cancer cell motility in vitro. These findings of this study will contribute to the establishment of a novel therapeutic antidote to MIBCs that are difficult to treat by regulating cancer-associated fibroblasts (CAFs) through targeting the identified pathway.

Free Research Field

膀胱がん

Academic Significance and Societal Importance of the Research Achievements

膀胱がんは、その周囲に存在する豊富な線維性間質を特徴としており、がん細胞とその周囲に存在するがん関連線維芽細胞との相互作用は、がんの浸潤・転移に重要な役割を持っているとされているが、その詳細は明らかではない。今回の研究により、膀胱癌と癌関連線維芽細胞の共培養におけるがん遊走能、浸潤能の亢進と、その経路をRAGE-Fc（RAGE阻害薬）によって阻害されることを見出した。これらの研究成果より癌自体を抑制するだけでなく、癌周囲の間質組織をターゲットとした治療を組み合わせることで、より有効な治療戦略の開発が期待され、RAGE-Fcは治療薬の候補としても期待できる。