Pten依存は,血液形成性幹細胞と白血病を誘発する細胞を区別する
Omer H Yilmaz1, Riccardo Valdez, Brian K Theisen
1Howard Hughes Medical Institute, Life Sciences Institute, Department of Internal Medicine, and Center for Stem Cell Biology, University of Michigan, Ann Arbor, Michigan 48109-2216, USA.
Nature
|April 7, 2006
まとめ
がん幹細胞と正常な血液形成幹細胞 (HSC) のメカニズム的差異をターゲットにすることで,効果的な治療法が得られます. HSCにおけるPtenの消去は白血病を引き起こしたが,がん細胞とは異なり,HSCの枯渇も引き起こし,この違いはラパミシンによって抑制された.
科学分野:
- 血液学 ヘマトロジ
- 癌生物学 癌生物学について
- 幹細胞生物学 幹細胞生物学
背景:
- 正常幹細胞とがん幹細胞は,機能的に類似している.
- 正常な幹細胞を傷つけることなく,がん幹細胞を選択的に除去する治療法を開発することは,重要な課題です.
研究 の 目的:
- 正常幹細胞とがん幹細胞のメカニズム的差異をターゲットにすることで,選択的がん治療につながるかどうかを調査する.
- PtenとmTOR経路が,正常な造血幹細胞 (HSC) の行動と白血病を誘発する細胞の区別における役割を決定する.
主な方法:
- マウスの成人血球形成細胞におけるPten腫瘍抑制遺伝子の条件付き削除.
- 骨髄増殖性疾患および移植性白血病の誘導.
- 造血幹細胞 (HSC) の増殖および再構成能力の評価.
- mTOR阻害剤であるラパミシンが,正常なHSCと白血病を誘発する細胞の両方に与える影響の評価.
主要な成果:
- 造血細胞におけるPtenの欠失により,骨髄増殖性疾患と白血病が急速に誘発された.
- Ptenの削除はHSCの増殖を促したが,逆説的にHSCの枯渇につながり,安定した再構成を防止した.
- 白血病を誘発する細胞は,HSCとは異なり,Pten.なしでも自らを維持することができる.
- ラパミシン治療は,Pten欠損誘発的効果を抑制し,白血病を誘発する細胞を枯渇させ,正常なHSC機能を回復させた.
結論:
- 正常なHSCと白血病を誘発する細胞の間には,特にPten依存性に関して,メカニズム的な違いがあります.
- mTOR経路は,これらの差異の重要な媒介であり,実行可能な治療目標を表しています.
- これらの特定の分子経路をターゲットにすることで,正常なHSC機能を保ちながら,がん幹細胞を選択的に排除する戦略が提供されます.
関連する概念動画
Cancer Stem Cells and Tumor Maintenance
Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
Hematopoiesis
The process of blood cell formation is called hematopoiesis. Hematopoiesis starts early during development, on the seventh day of embryogenesis. This phase of hematopoiesis is called the primitive wave, wherein the extraembryonic yolk sac allows the production of erythroid cells and endothelial cells from a common precursor called hemangioblast. The erythroid cells provide oxygen to support the growth of the rapidly dividing embryo. Hemangioblasts later develop into hematopoietic stem cells or...
Multipotency of Hematopoietic Stem Cells
The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...
Lineage Commitment
Commitment is the process whereby stem cells:
Regulation of Hematopoietic Stem Cells
All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
Source And Potency Of Stem Cells
Stem cells are undifferentiated cells with extensive self-renewal properties that help them maintain their population during the fetal and adult stages of life. They can specialize in all cell types of the human body. However, their differential potential may vary and can be classified into five types. Stem cells can be (1) Totipotent, (2) Pluripotent, (3) Multipotent, (4) Oligopotent, and (5) Unipotent. Each stem cell has a specific origin; the fertilized egg or zygote is a totipotent cell and...


