相关实验视频

Updated: Jun 19, 2025

A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth

A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth

Published on: December 22, 2020

纤维细胞在结肠直肠癌细胞中促进对KRAS沉默的抵抗

Susana Mendonça Oliveira^1,2,3,4, Patrícia Dias Carvalho^1,2,5, André Serra-Roma^1,2

¹i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.

|July 27, 2024

概括

与癌症相关的纤维细胞 (CAFs) 可以在结直肠癌 (CRC) 中驱动对KRAS向治疗的耐药性. CAF分泌体恢复癌症干细胞标记物并促进瘤促进途径,这表明外部因素有助于治疗失败.

科学领域:

在瘤学瘤学.
癌症生物学癌症生物学
分子向疗法分子向疗法

背景情况:

大肠直肠癌 (CRC) 对针对KRAS的向疗法的反应有限.
在CRC中抵抗KRAS抑制的机制尚未完全理解.

研究的目的:

调查癌症相关纤维细胞 (CAFs) 秘密体在调解CRC中对KRAS沉默的抵抗中的作用.
探索CAF分泌的因素如何影响癌症干细胞特性和KRAS抑制的CRC细胞中的信号通路.

主要方法:

CRC细胞系 (HCT15,HCT116,SW480) 在正常或CAF调节的介质中进行培养.
流细胞计分析了干细胞标志物表达 (CD24,CD49f,CD104).
球体形成试验评估了干细胞的潜力.
RNA测序 (RNAseq) 分析了用CAF受条件介质治疗的KRAS沉默细胞中的基因表达.

主要成果:

KRAS静音降低了干细胞标记物表达和球形形成效率.
由CAF分泌的因子逆转了这些效应,恢复了干细胞标记物并增加了干细胞性.
RNAseq揭示了CAF因子对KRAS沉默细胞的瘤原生途径 (KRAS,TGFβ,NOTCH,WNT,MYC,EMT) 的上调.

结论:

对CRC中KRAS向抑制的抵抗可能涉及细胞内在因素和来自瘤微环境的外部信号,特别是CAF分泌体.
纤维细胞分泌的因素可以促进干性和激活瘤性途径,从而导致治疗耐药性.

关键词:

克拉斯 (Kras) 是一个国家.癌症的茎性癌症的茎性结肠直肠癌是什么意思表皮细胞-介质细胞过渡.纤维细胞的细胞.治疗耐药性治疗耐药性

更多相关视频

Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes

Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes

Published on: June 3, 2018

A Multiplexed Luciferase-based Screening Platform for Interrogating Cancer-associated Signal Transduction in Cultured Cells

A Multiplexed Luciferase-based Screening Platform for Interrogating Cancer-associated Signal Transduction in Cultured Cells

Published on: July 3, 2013

相关概念视频

Introduction to Fibroblasts

Introduction to Fibroblasts

Rudolph Virchow discovered spindle-shaped cells called fibroblasts in 1858. Inactive fibroblasts, called fibrocytes, become activated by various stimuli, such as growth factors and inflammatory cytokines. Activated fibroblasts play a crucial role in wound healing, inflammation, formation of new blood vessels, and cancer progression. Uncontrolled activation of fibroblasts results in fibrosis, the excess deposition of fibrous tissue, which can lead to scarring and affect normal organs. This...

Treatment Resistant Cancers

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...

The Ras Gene

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...