Dying tumor cells stimulate proliferation of living tumor cells via caspase‐dependent protein kinase Cδ activation in pancreatic ductal adenocarcinoma

作者：Jin Cheng, Ling Tian, Jingjing Ma, Yanping Gong, Zhengxiang Zhang, Zhiwei Chen, Bing Xu, Hui Xiong, Chuan‐Yuan Li, Qian Huang · 发表于：Molecular Oncology · 年份：2014 · DOI：10.1016/j.molonc.2014.07.024 · 被引用次数：101 · 研究领域：Cell death mechanisms and regulation、Pancreatic and Hepatic Oncology Research、Liver physiology and pathology

Pancreatic cancer is one of the most lethal human cancers, and radiotherapy is often implemented for locally advanced pancreatic ductal adenocarcinoma. Tumor cell repopulation is a major challenge in treating cancers after radiotherapy. In order to address the problem of tumor repopulation, our previous studies have demonstrated that dying cells stimulate the proliferation of living tumor cells after radiotherapy. In particular, dying cells undergoing apoptosis also activate survival or proliferation signals and release growth factors to surrounding living cells. In the present study, we used an in vitro model to examine the possible mechanisms for dying cell stimulated tumor repopulation in pancreatic cancer. In this model, a small number of living, luciferase-labeled pancreatic cancer cells (reporter) were seeded onto a layer of a much larger number of irradiated, unlabeled pancreatic cancer cells and the growth of the living cells was measured over time as a gage of tumor repopulation. Our results indicate that irradiated, dying Panc1 feeder cells significantly stimulated the proliferation of living Panc1 reporter cells. Importantly, we identified that the percentage of apoptotic cells and the cleavage of caspases 3 and 7 and protein kinase Cδ (PKCδ) were increased in irradiated Panc1 cells. We presumed that caspases 3 and 7 and PKCδ as integral mediators in the process of dying pancreatic cancer cell stimulation of living tumor cell growth. In order to demonstrate the imp...