Meyer Nicole, Hinz Nicole, Schumacher Anne, Weißenborn Christine, Fink Beate, Bauer Mario, von Lenthe Sophie, Ignatov Atanas, Fest Stefan, Zenclussen Ana Claudia
Experimental Obstetrics and Gynecology, Medical Faculty, Otto-von-Guericke University Magdeburg, 39108 Magdeburg, Germany.
Department of Environmental Immunology, UFZ-Helmholtz Centre for Environmental Research Leipzig-Halle, 04318 Leipzig, Germany.
Cancers (Basel). 2023 Aug 26;15(17):4278. doi: 10.3390/cancers15174278.
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-Kit (Kit) mice. Reconstitution of Kit was 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 Kit mice resulted in significantly increased tumor growth compared to C57BL6/J mice. Injection of BMMCs into Kit mice 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。一个复杂的网络，包括肿瘤与免疫细胞之间的相互作用，调节着肿瘤微环境、生存和生长。肥大细胞（MCs）在卵巢肿瘤病理生理学中的作用尚不清楚。我们旨在通过体外和体内方法了解MCs对肿瘤细胞迁移和生长的影响。使用人肿瘤细胞系（SK-OV-3、OVCAR-3）和人MCs（HMC-1）进行了伤口愈合试验。将小鼠ID8肿瘤细胞注射到C57BL6/J野生型（WT）和MC缺陷型C57BL/6-Kit（Kit）小鼠体内。通过转移野生型骨髓来源的MCs（BMMCs）进行Kit重建。通过高频超声记录肿瘤发展情况。在体外，我们观察到人类卵巢肿瘤细胞在直接或间接与MC接触后迁移减少。在体内，与C57BL6/J小鼠相比，将ID8细胞注射到Kit小鼠体内导致肿瘤生长显著增加。将BMMCs注射到Kit小鼠体内可重建MCs并恢复肿瘤生长。我们的数据表明，MCs对卵巢肿瘤生长具有抑制作用，可能成为一个新的治疗靶点。
