Breast cancer is the leading cause of death among females in developed countries. Although the implementation of screening tests and the development of new therapies have increased the probability of remission, relapse rates remain high. Numerous studies have indicated the connection between cancer-initiating cells and slow cellular cycle cells, identified by their capacity to retain long labeling (LT+). In this study, we perform new assays showing how stem cell self-renewal modulating proteins, such as PEDF, can modify the properties, percentage of biomarker-expressing cells, and carcinogenicity of cancer stem cells. The PEDF signaling pathway could be a useful tool for controlling cancer stem cells’ self-renewal and therefore control patient relapse, as PEDF enhances resistance in breast cancer patient cells’ in vitro culture. We have designed a peptide consisting of the C-terminal part of this protein, which acts by blocking endogenous PEDF in cell culture assays. We demonstrate that it is possible to interfere with the self-renewal capacity of cancer stem cells, induce anoikis in vivo, and reduce resistance against docetaxel treatment in cancer patient cells in in vitro culture. We have also demonstrated that this modified PEDF protein produces a significant decrease in the percentage of expressed cancer stem cell markers.
乳腺癌是发达国家女性死亡的首要原因。尽管筛查检测的实施和新疗法的开发提高了缓解概率，但复发率仍然居高不下。大量研究表明，癌症起始细胞与慢周期细胞之间存在关联，后者通过其长期标记保留能力（LT+）得以识别。本研究通过新实验表明，干细胞自我更新调节蛋白（如PEDF）能够改变癌症干细胞的特性、生物标志物表达细胞比例及致癌性。PEDF信号通路可作为调控癌症干细胞自我更新的有效工具，从而控制患者复发，因为PEDF能增强乳腺癌患者细胞体外培养的耐药性。我们设计了一种由该蛋白C末端组成的多肽，在细胞培养实验中通过阻断内源性PEDF发挥作用。实验证明，该多肽能够干扰癌症干细胞的自我更新能力，在体内诱导失巢凋亡，并在体外培养中降低癌症患者细胞对多西他赛治疗的耐药性。我们还证实，这种修饰后的PEDF蛋白能显著降低癌症干细胞标志物的表达比例。
Self-Renewal Inhibition in Breast Cancer Stem Cells: Moonlight Role of PEDF in Breast Cancer
肿瘤(癌症)患者之家