腫瘍増殖の非細胞自律的誘導は,サブクローン異質性を支持する

Andriy Marusyk¹, Doris P Tabassum², Philipp M Altrock³

¹1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA [3] Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.

Nature

|August 1, 2014

まとめ

腫瘍の成長には,体的進化とサブクローン異質性が含まれます. 少数の細胞亜集団は腫瘍の拡大を促すことができるが,競争に追いやられ,崩壊につながり,相互作用は異質性を安定させる.

科学分野:

腫瘍学腫瘍学
進化生物学の進化生物学について
数学生物学数学生物学について

背景:

がんは体的進化を経て発症し,腫瘍内において重大なサブクローン異質性が生じます.
サブクローンの共存を促すメカニズムとその生物学的影響は十分に理解されていません.

研究の目的:

マウスの異種移植モデルを使用して,腫瘍フェノタイプとクローン競争に対するサブクローン異質性の影響を調査する.
数学的なモデリングを通じて,腫瘍内クローン異質性の生成を制御するルールを特定する.

主な方法:

腫瘍の成長動態を研究するためにマウスの異種移植モデルを使用した.
クローン相互作用と異質性を分析するための数学的モデリングフレームワークを開発しました.

主要な成果:

腫瘍の成長は,環境的制約を克服し,全体的な増殖を促進する小さな亜集団によって推進される可能性があります.
この駆動サブポポレーションは,より速く成長するクローンによって競争に追い出され,腫瘍の崩壊につながります.
非細胞自律的成長とクローン干渉は,サブクローン異質性を安定させることが判明しました.

結論:

サブクローン異質性は,腫瘍の進行と競争力ダイナミクスにおいて重要な役割を果たします.
非細胞自律的な成長とクローン干渉によって安定したクロン間相互作用は,新しい現象型特性の出現につながる可能性があります.

さらに関連する動画

10:13

Non-Destructive Evaluation of Regional Cell Density Within Tumor Aggregates Following Drug Treatment

Published on: June 21, 2022

1.7K

07:18

Isolation and Characterization of Tumor-initiating Cells from Sarcoma Patient-derived Xenografts

Published on: June 13, 2019

8.5K

関連する概念動画

02:40

Cancer Stem Cells and Tumor Maintenance

4.3K

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...

4.3K

02:40

Cancer Stem Cells and Tumor Maintenance

2.0K

02:53

Adaptive Mechanisms in Cancer Cells

5.7K

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...

5.7K

02:18

Cancer

51.4K

Cancers arise due to mutations in genes involved in the regulation of cell division, which leads to unrestricted cell proliferation. Modern science and medicine have made great strides in the understanding and treatment of cancer, including eradicating cancer in some patients. However, there is still no cure for cancer. This is largely due to the fact that cancer is a large group of many diseases.

51.4K

02:07

Tumor Progression

6.2K

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...

6.2K

02:21

Cancers Originate from Somatic Mutations in a Single Cell

12.4K

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...