TrkB介导胰腺癌转移性干细胞大聚集体形成及转移机制的研究

Our previous study revealed that distant metastasis of pancreatic cancer cells rely on TrkB mediated formation of large aggregates. Aggregation of tumor cells in the body by autophagy against the selective pressure from the environment and anoikis occurred. what is more interesting is at the core of the large tumor cell aggregates may have a stem cell-like characteristics. We found that such features may be derived from the fusion of the cancer cells that with high expression of TrkB migrating to bone marrow stem cell or tissue existence itself. peripheral localization of the tumor cells seems to cooperate with each other to protect the core stem cell-like tumor cells transferring to the target organ acting as the Trojan horse (For example, enhancing the integrity of the aggregates by Interophagy, releasing microvesicles that expressing high TrkB to interfere immunity). This study will verify that the cell fusion mediated by TrkB is the key factor for the large aggregates acquiring the characteristics of stem cell. The inhibition of TrkB signaling pathways may interfere cell fusion, destructing the structure of the large aggregates and the microvesicles for inhibiting cancer metastasis.

我们既往研究发现胰腺癌的远处转移依赖于TrkB所介导的癌细胞大聚集体的形成，聚集体中的肿瘤细胞可以通过自体吞噬(Autophagy)对抗来自环境的选择性压力以及失巢凋亡(Anoikis)的发生。更为有趣的是，处于核心的肿瘤细胞似具有干细胞样特征，我们发现这种特征可能与高表达TrkB的肿瘤细胞与骨髓迁徙来的干细胞或本身组织存在的干细胞诱导融合有关。并且聚集体周围的肿瘤细胞似通过相互协作成为保护核心干细胞样瘤细胞转移到靶器官的特洛伊木马（Trojan horse）（如可能通过互噬Interophagy增强聚集体完整性，释放表达TrkB的微囊泡Microvesicles干扰免疫等）。本研究将在我们既往研究基础上进一步验证TrkB介导的细胞融合是胰腺癌转移聚集体中肿瘤细胞获得干细胞特性的途径，对TrkB信号途径的抑制可能通过干扰细胞融合，破坏大聚集体结构以及微囊泡的释放而达到抑制肿瘤转移的发生。