在STK11/LKB1突变的NSCLC中的癌症白内障依赖于瘤分泌的GDF15
bioRxiv : the preprint server for biology
|July 1, 2024
概括
在NSCLC中STK11/LKB1的损失通过高GDF15.1驱动缓解症. 向GDF15在临床前模型中抑制了消耗,将其确定为癌症缓解症的关键治疗标.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 代谢疾病 代谢疾病
背景情况:
- 卡切西亚是一种复杂的消耗综合征,其特征是脂肪组织和肌肉质量的损失,经常在癌症患者中观察到.
- 在STK11/LKB1中功能丧失突变,这是AMP激活蛋白激酶的关键调节者,与癌症缓解症 (CC) 和非小细胞肺癌 (NSCLC) 的体重减轻有关.
- 增长分化因子15 (GDF15) 是一种新兴的因子,与NSCLC患者的缓冲症相关.
研究的目的:
- 为了研究GDF15在STK11/LKB1突变NSCLC相关的缓解症中的作用.
- 确定GDF15是否在这种情况下是缓解症的调解者,以及它是否代表了一个可行的治疗点.
主要方法:
- 在患者衍生和基因工程STK11/LKB1突变NSCLC模型中GDF15表达的表征.
- 在体内给予GDF15中和抗体,以评估对缓解症表型的影响.
- 在NSCLC细胞系中抑制GDF15,以评估其对于缓解症诱导的必要性.
- 在突变的NSCLC系中复制野生型STK11/LKB1以观察GDF15和缓解症的影响.
主要成果:
- 瘤mRNA和血清GDF15水平在患有STK11/LKB1-突变NSCLC的小鼠中显著升高.
- 在临床前模型中,GDF15中和抑制了脂肪损失,肌肉缩和体重减轻.
- GDF15沉默了废弃的缓解症诱导,表明瘤衍生的GDF15是主要来源.
- 恢复STK11/LKB1功能挽救了缓冲症和正常化的GDF15水平.
结论:
- 由瘤分泌的GDF15是具有STK11/LKB1功能丧失突变的NSCLC中缓解症的关键调解者.
- 在这种患者群体中,GDF15代表了一种有前途的治疗标来对抗癌症缓解症.
更多相关视频
06:51Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
Published on: July 21, 2018
17.9K
06:35A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth
Published on: December 22, 2020
4.4K
相关概念视频
02:17The Tumor Microenvironment
6.6K
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...
6.6K
02:40Cancer Stem Cells and Tumor Maintenance
4.9K
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...
4.9K
02:53Adaptive 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,...
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