Metabolic reprogramming of cancer-associated fibroblasts in pancreatic cancer contributes to the intratumor heterogeneity of PET-CT.
Metabolic reprogramming of cancer-associated fibroblasts in pancreatic cancer contributes to the intratumor heterogeneity of PET-CT.
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DOI：
10.1016/j.csbj.2023.04.003
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发表时间：
2023
影响因子：
6
通讯作者：
Xu, Jin
中科院分区：
文献类型：
--
作者：
Meng, Qingcai;Fang, Zengli;Mao, Xiaoqi;Tang, Rong;Liang, Chen;Hua, Jie;Wang, Wei;Shi, Si;Yu, Xianjun;Xu, Jin
正电子发射断层扫描-计算机断层扫描（PET-CT）的肿瘤内异质性通过不同的18f -氟脱氧葡萄糖（FDG）摄取来反映。越来越多的证据表明，肿瘤和非肿瘤成分可以影响肿瘤中18F-FDG的总摄取。癌相关成纤维细胞（cancer -associated fibroblasts, CAFs）被认为是胰腺癌肿瘤微环境（tumor microenvironment， TME）中主要的非肿瘤性成分。我们的研究旨在探讨cas代谢变化对PET-CT异质性的影响。126例胰腺癌患者在治疗前接受了PET-CT和内镜超声弹性成像（EUS-EG）检查。PET-CT最大标准化摄取值（SUVmax）高与eus衍生应变比（SR）呈正相关，提示患者预后较差。此外，单细胞RNA分析显示，在胰腺癌成纤维细胞中，CAV1影响糖酵解活性并与糖酵解酶表达相关。我们还通过免疫组化（IHC）方法观察了suvmax -高组和suvmax -低组胰腺癌患者肿瘤间质中CAV1与糖酵解酶的表达呈负相关。此外，具有高糖酵解活性的cas有助于胰腺癌细胞迁移，阻断CAF糖酵解逆转了这一过程，表明糖酵解的cas促进了胰腺癌的恶性生物学行为。总之，我们的研究表明，cas的代谢重编程影响肿瘤中18F-FDG的总摄取。因此，糖酵解性CAFs的增加与CAV1表达的降低促进了肿瘤的进展，高SUVmax可能是针对肿瘤间质进行治疗的标志。进一步的研究应阐明潜在的机制。
Intratumor heterogeneity of positron emission tomography-computed tomography (PET-CT) is reflected by variable 18F-fluorodeoxyglucose (FDG) uptake. Increasing evidence has shown that neoplastic and non-neoplastic components can affect the total 18F-FDG uptake in tumors. Cancer-associated fibroblasts (CAFs) is considered as the main non-neoplastic components in tumor microenvironment (TME) of pancreatic cancer. Our study aims to explore the impact of metabolic changes in CAFs on heterogeneity of PET-CT. A total of 126 patients with pancreatic cancer underwent PET-CT and endoscopic ultrasound elastography (EUS-EG) before treatment. High maximum standardized uptake value (SUVmax) from the PET-CT was positively correlated with the EUS-derived strain ratio (SR) and indicated poor prognosis of patients. In addition, single-cell RNA analysis showed that CAV1 affected glycolytic activity and correlated with glycolytic enzyme expression in fibroblasts in pancreatic cancer. We also observed the negative correlation between CAV1 and glycolytic enzyme expression in the tumor stroma by using immunohistochemistry (IHC) assay in the SUVmax-high and SUVmax-low groups of pancreatic cancer patients. Additionally, CAFs with high glycolytic activity contributed to pancreatic cancer cell migration, and blocking CAF glycolysis reversed this process, suggesting that glycolytic CAFs promote malignant biological behavior in pancreatic cancer. In summary, our research demonstrated that the metabolic reprogramming of CAFs affects total 18F-FDG uptake in tumors. Thus, an increase in glycolytic CAFs with decreased CAV1 expression promotes tumor progression, and high SUVmax may be a marker for therapy targeting the neoplastic stroma. Further studies should clarify the underlying mechanisms.
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