| Project/Area Number |
21K20824
|
|---|
| Research Category |
Grant-in-Aid for Research Activity Start-up
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
0901:Oncology and related fields
|
|---|
| Research Institution | University of Tsukuba |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2021-08-30 – 2023-03-31
|
| Project Status |
Completed (Fiscal Year 2022)
|
| Budget Amount *help |
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
|---|
| Keywords | 膵癌 / 癌関連線維芽細胞 / 腫瘍微小環境 / CAF / 糖鎖 |
|---|
| Outline of Research at the Start |
難治性固形癌の代表である膵癌の病理組織学的な特徴である間質組織増生に焦点を当て、
その中心的な役割を担う腫瘍関連線維芽細胞(Cancer Associated Fibroblast, CAF)の特徴・機能を糖鎖構造解析という新たな手法を用いて理解する。CAFは癌細胞を守るバリアになり抗癌剤抵抗性の原因となる。本研究ではCAF特異的な糖鎖構造と、その糖鎖と結合するレクチンを同定し、臨床膵癌由来のCAFとオルガノイドを用いてその特異性と機能を検証する。本研究成果は後のLDC作製へと発展させ、CAFリプログラミングを誘導しCAFによる薬剤バリアを除去する、新規CAF糖鎖標的治療薬の開発を目指す。
|
| Outline of Final Research Achievements |
Cancer-associated fibroblasts (CAFs) obtained by primary culture of clinical specimens (CAFs derived from clinical specimens), CAFs obtained by direct co-culture of adipose-derived mesenchymal stem cells (AD-MSCs) with pancreatic cancer cell lines (DR-CAFs), and CAFs obtained by indirect co-culture (TW-CAFs) were comprehensively searched for CAF-specific sugar chains by We also comprehensively searched for CAF-specific glycans using lectin microarrays to identify CAF-specific glycans in clinical pancreatic cancer tissues. In addition, lectin staining was performed on clinical pancreatic cancer tissues, and candidate CAF-specific glycans were extracted based on differences in staining intensity. The extracted lectin candidates were compared with RNA-seq data obtained in previous studies, and no candidate lectins were found to be differentially expressed in pancreatic cancer cells, normal fibroblasts, and CAFs.
|
| Academic Significance and Societal Importance of the Research Achievements |
今回用いたレクチンマイクロアレイで抽出した候補の糖鎖構造については、RNA-seqで特異性の裏付けはとれなかった。昨今注目されているCAF heterogeneityがこの結果に影響している可能性が高い。一細胞解析技術が発展しているので、この技術を用いてCAF heterogeneityの詳細を調べることができれば、CAF特異的なタンパクや糖鎖を同定することが可能であると考える。
|
