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排卵源凝血蛋白酶级联和肝细胞生长因子支持生理生长和恶性转化。

Ovulation sources coagulation protease cascade and hepatocyte growth factor to support physiological growth and malignant transformation.

机构信息

Center for Prevention and Therapy of Gynecological Cancers, Department of Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan, ROC.

Department of Obstetrics & Gynecology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan, ROC.

出版信息

Neoplasia. 2021 Nov;23(11):1123-1136. doi: 10.1016/j.neo.2021.09.006. Epub 2021 Oct 21.

DOI:10.1016/j.neo.2021.09.006
PMID:34688971
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8550993/
Abstract

The fallopian tube fimbrial epithelium, which is exposed to the follicular fluid (FF) contents of ovulation, is regarded as the main origin of ovarian high-grade serous carcinoma. Previously, we found that growth factors in FF, such as IGF2, are responsible for the malignant transformation of fallopian tube epithelium. However, ovulation is a monthly transient event, whereas carcinogenesis requires continuous, long-term exposure. Here, we found the transformation activity of FF sustained for more than 30 days after drainage into the peritoneal fluid (PF). Hepatocyte growth factor (HGF), activated through the ovulation injury-tissue factor-thrombin-HGF activator (HGFA)-HGF cleavage cascade confers a sustained transformation activity to fallopian tube epithelium, high-grade serous carcinoma. Physiologically, the high reserve of the coagulation-HGF cascade sources a sustained level of HGF in PF, then to the blood circulation. This HGF axis promotes the growth of the corpus luteum and repair of tissue injury after ovulation.

摘要

输卵管伞端的纤毛上皮暴露于排卵时的卵泡液（FF）内容物中，被认为是卵巢高级别浆液性癌的主要起源。此前，我们发现 FF 中的生长因子，如 IGF2，负责输卵管上皮的恶性转化。然而，排卵是每月的短暂事件，而癌变需要持续的、长期的暴露。在这里，我们发现 FF 的转化活性在排入腹腔液（PF）后持续超过 30 天。通过排卵损伤-组织因子-凝血酶-HGF 激活物（HGFA）-HGF 切割级联激活的肝细胞生长因子（HGF）赋予输卵管上皮、高级别浆液性癌持续的转化活性。从生理上讲，凝血-HGF 级联的高储备在 PF 中产生持续水平的 HGF，然后进入血液循环。该 HGF 轴促进黄体的生长和排卵后组织损伤的修复。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe21/8550993/11d0d969e317/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe21/8550993/2182ecdd84c4/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe21/8550993/eb6d07ceb1a5/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe21/8550993/2d2e43095c47/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe21/8550993/32b27cbf08f5/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe21/8550993/63f97787e139/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe21/8550993/41251f6de1a0/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe21/8550993/553b129cea0b/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe21/8550993/fab906676412/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe21/8550993/11d0d969e317/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe21/8550993/2182ecdd84c4/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe21/8550993/eb6d07ceb1a5/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe21/8550993/2d2e43095c47/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe21/8550993/32b27cbf08f5/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe21/8550993/63f97787e139/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe21/8550993/41251f6de1a0/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe21/8550993/553b129cea0b/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe21/8550993/fab906676412/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe21/8550993/11d0d969e317/gr9.jpg

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