Versican secreted by the ovary links ovulation and migration in fallopian tube derived serous cancer.
Versican secreted by the ovary links ovulation and migration in fallopian tube derived serous cancer.
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卵巢分泌的多功能蛋白聚糖与输卵管衍生浆液性癌的排卵和迁移有关。
DOI：
10.1016/j.canlet.2022.215779
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发表时间：
2022-09-01
期刊：
影响因子：
9.7
通讯作者：
Burdette, Joanna E.
中科院分区：
文献类型：
--
作者：
Russo, Angela;Yang, Zizhao;Heyrman, Georgette Moyle;Cain, Brian P.;Carrero, Alfredo Lopez;Isenberg, Brett C.;Dean, Matthew J.;Coppeta, Jonathan;Burdette, Joanna E.
高级别浆液性卵巢癌（HGSOC）主要发生在输卵管上皮（FTE）中，并在进一步转移到腹膜之前首先定殖于卵巢。卵巢癌的风险与排卵次数直接相关，这表明卵巢可能分泌特定的因子，在排卵期间作为输卵管源性肿瘤细胞的化学引诱物。我们发现，3D卵巢器官培养产生了一种分泌因子，该因子增强了FTE非致瘤细胞的迁移，以及在高级别浆液性癌中常见的具有特定途径修饰的细胞。通过大小分级和小分子抑制剂筛选，确定分泌蛋白的大小为50- 100 kDa，并通过表皮生长因子受体（EGFR）起作用。为了将候选者与排卵相关联，对PREDICT器官芯片系统进行了优化，以在灌注的微流体平台中支持排卵。Versican被发现在正确的分子量范围内，含有EGF样结构域，并被发现与排卵的预测系统。外源性多功能蛋白聚糖以EGFR依赖性方式增加小鼠和人FTE细胞的迁移、侵袭并增强其与卵巢的粘附。鉴定排卵期间分泌的影响FTE细胞定殖卵巢能力的蛋白质为限制原发性卵巢转移的策略的发展提供了新的见解。
High grade serous ovarian cancers (HGSOC) predominantly arise in the fallopian tube epithelium (FTE) and colonize the ovary first before further metastasis to the peritoneum. Ovarian cancer risk is directly related to the number of ovulations, suggesting that the ovary may secrete specific factors that act as chemoattractants for fallopian tube derived tumor cells during ovulation. We found that 3D ovarian organ culture produced a secreted factor that enhanced the migration of FTE non-tumorigenic cells as well as cells harboring specific pathway modifications commonly found in high grade serous cancers. Through size fractionation and a small molecule inhibitors screen, the secreted protein was determined to be 50–100kDa in size and acted through the Epidermal Growth Factor Receptor (EGFR). To correlate the candidates with ovulation, the PREDICT organ-on-chip system was optimized to support ovulation in a perfused microfluidic platform. Versican was found in the correct molecular weight range, contained EGF-like domains, and was found to correlate with ovulation in the PREDICT system. Exogenous versican increased migration, invasion, and enhanced adhesion of both murine and human FTE cells to the ovary in an EGFR-dependent manner. The identification of a protein secreted during ovulation that impacts the ability of FTE cells to colonize the ovary provides new insights into the development of strategies for limiting primary ovarian metastasis.
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影响因子：
3.9
作者：
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