一种多细胞机械化学模型,用于研究瘤微环境重塑和前转移性位形成
Shreyas U Hirway1, Kylie G Nairon1, Aleksander Skardal1
1Department of Biomedical Engineering, The Ohio State University, Columbus, OH USA.
Cellular and molecular bioengineering
|February 10, 2025
概括
计算建模揭示了生长因子的可用性和细胞外矩阵度是结直肠癌肝脏转移中前转移性利基形成的关键驱动因素. 这些因素影响了瘤的侵入性和在二级环境中的殖民.
科学领域:
- 计算生物学是一种计算生物学.
- 癌症研究 癌症研究
- 细胞动态 细胞动态
背景情况:
- 结肠直肠癌 (CRC) 转移到肝脏是癌症相关死亡的一个重要原因.
- 转移前位 (PMN) 形成对于二次部位的瘤定居至关重要.
- PMN的发展涉及到肝细胞的激活,如星状细胞和库普弗细胞,重塑细胞外基质 (ECM).
研究的目的:
- 使用多细胞计算模型研究PMN形成的时空动态.
- 描述关键因素对PMN发展和瘤侵入性的影响.
主要方法:
- 开发了一个细胞模型,集成细胞内/细胞外信号,细胞力和多种细胞类型.
- 进行了数值实验,以评估生长因子度的影响,瘤到达时间,细胞组成和群大小.
主要成果:
- 确定了生长因子的可用性和ECM度作为瘤侵入性的主要决定因素.
- 预测ECM度潜力和星状细胞生长因子敏感性对于PMN形成和ECM重塑至关重要.
结论:
- 开发的计算框架推进了对癌症转移的模拟.
- 突出了环境因素和特定细胞敏感性在转移前位形成中的关键作用.
相关概念视频
The Tumor Microenvironment
6.5K
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
6.5K
Metastasis
5.5K
Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
5.5K


