High grade serous ovarian cancer (HGSOC) is the fifth leading cause of cancer deaths among women. New evidence suggests that HGSOC arises in the fallopian tube and then colonizes the ovary before spreading into the peritoneal space. Therefore, due to the proximity of this metastasis, an experimental design was optimized using imaging mass spectrometry to capture the spatial composition of small molecules uniquely expressed when fallopian-tube-derived tumor cells were grown in the microenvironment of the ovary as a model of primary metastasis. The observed mass-to-charge ratios (m/z’s) that were induced specifically in coculture represent small molecules that may contribute to the metastasis of HGSOC selectively to the ovary. Human fallopian tube epithelial HGSOC and tumorigenic murine oviductal epithelial cells, but not normal cell types, repeatedly induced a signal from the ovary at m/z 170. This signal was identified as norepinephrine, which was confirmed to stimulate invasion of ovarian cancer cells lacking wild-type p53. These molecules may reveal pathways that contribute to metastasis and biological targets for therapeutic intervention to block ovarian metastasis of fallopian-tube-derived HGSOC. The developed mass spectrometry method can be adapted to other mammalian-based model systems for investigation of untargeted metabolomics that facilitate metastasis.

中文翻译：

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成像质谱揭示了输卵管和卵巢之间的串扰，该串扰驱动卵巢癌的原发转移

高度浆液性卵巢癌（HGSOC）是女性中导致癌症死亡的第五大主要原因。新证据表明，HGSOC发生在输卵管中，然后在卵巢扩散到腹膜腔之前先在卵巢中定植。因此，由于这种转移的临近性，使用成像质谱法对实验设计进行了优化，以捕获当输卵管来源的肿瘤细胞在卵巢的微环境中作为原发性模型生长时唯一表达的小分子的空间组成。转移。观察到的质荷比（m / z在共培养物中被特异性诱导的α-β-α-β-谷胱甘肽代表可能有助于HGSOC选择性转移到卵巢的小分子。人输卵管上皮细胞HGSOC和致癌鼠输卵管上皮细胞（而非正常细胞类型）反复在m / z处诱导出来自卵巢的信号170.该信号被确认为去甲肾上腺素，已证实可刺激缺乏野生型p53的卵巢癌细胞的侵袭。这些分子可能揭示有助于转移的途径和治疗干预的生物学靶标，以阻止输卵管衍生的HGSOC的卵巢转移。所开发的质谱方法可以适用于其他基于哺乳动物的模型系统，以研究促进转移的非靶向代谢组学。