Ovarian cancer has the highest mortality rate among female reproductive tract malignancies. A complex network, including the interaction between tumor and immune cells, regulates the tumor microenvironment, survival, and growth. The role of mast cells (MCs) in ovarian tumor pathophysiology is poorly understood. We aimed to understand the effect of MCs on tumor cell migration and growth using in vitro and in vivo approaches. Wound healing assays using human tumor cell lines (SK-OV-3, OVCAR-3) and human MCs (HMC-1) were conducted. Murine ID8 tumor cells were injected into C57BL6/J wildtype (WT) and MC-deficient C57BL/6-KitW-sh/W-sh(KitW-sh) mice. Reconstitution of KitW-shwas performed by the transfer of WT bone marrow-derived MCs (BMMCs). Tumor development was recorded by high-frequency ultrasonography. In vitro, we observed a diminished migration of human ovarian tumor cells upon direct or indirect MC contact. In vivo, application of ID8 cells into KitW-shmice resulted in significantly increased tumor growth compared to C57BL6/J mice. Injection of BMMCs into KitW-shmice reconstituted MCs and restored tumor growth. Our data show that MCs have a suppressive effect on ovarian tumor growth and may serve as a new therapeutic target.
卵巢癌在女性生殖道恶性肿瘤中死亡率最高。肿瘤微环境、生存及生长受复杂网络调控，其中包括肿瘤细胞与免疫细胞间的相互作用。目前对肥大细胞在卵巢肿瘤病理生理学中的作用知之甚少。本研究旨在通过体外和体内实验探究肥大细胞对肿瘤细胞迁移与生长的影响。实验采用人源肿瘤细胞系（SK-OV-3、OVCAR-3）与人源肥大细胞系（HMC-1）进行划痕愈合实验。将小鼠ID8肿瘤细胞分别注射至C57BL6/J野生型小鼠及肥大细胞缺陷型C57BL/6-KitW-sh/W-sh小鼠体内，并通过移植野生型骨髓源性肥大细胞对KitW-sh小鼠进行细胞重建。采用高频超声记录肿瘤发展进程。体外实验显示，无论直接或间接接触肥大细胞，人卵巢肿瘤细胞的迁移能力均显著减弱。体内实验表明，与C57BL6/J小鼠相比，ID8细胞在KitW-sh小鼠体内肿瘤生长显著加速；而通过骨髓源性肥大细胞重建KitW-sh小鼠的肥大细胞后，肿瘤生长恢复至野生型水平。本研究证实肥大细胞对卵巢肿瘤生长具有抑制作用，可能成为新的治疗靶点。
Mast Cells Retard Tumor Growth in Ovarian Cancer: Insights from a Mouse Model
肿瘤(癌症)患者之家