Abstract

Lymphatic vasculature has been shown to promote metastatic spread of breast cancer. Lymphatic vasculature, which is made up of larger collecting vessels and smaller capillaries, has specialized cell junctions that facilitate cell intravasation. Normally, these junctions are designed to collect immune cells and other cellular components for immune surveillance by lymph nodes, but they are also utilized by cancer cells to facilitate metastasis. Although lymphatic development overall in the body has been well-characterized, there has been little focus on how the lymphatic network changes in the mammary gland during stages of remodeling such as pregnancy, lactation, and postpartum involution. In this review, we aim to define the currently known lymphangiogenic factors and lymphatic remodeling events during mammary gland morphogenesis. Furthermore, we juxtapose mammary gland pubertal development and postpartum involution to show similarities of pro-lymphangiogenic signaling as well as other molecular signals for epithelial cell survival that are critical in these morphogenic stages. The similar mechanisms include involvement of M2-polarized macrophages that contribute to matrix remodeling and vasculogenesis; signal transducer and activator of transcription (STAT) survival and proliferation signaling; and cyclooxygenase 2 (COX2)/Prostaglandin E2 (PGE2) signaling to promote ductal and lymphatic expansion. Investigation and characterization of lymphangiogenesis in the normal mammary gland can provide insight to targetable mechanisms for lymphangiogenesis and lymphatic spread of tumor cells in breast cancer.

中文翻译：

---

正常发育和肿瘤相关重塑过程中乳腺淋巴管系统的表征

摘要

淋巴管系统已被证明可促进乳腺癌的转移扩散。淋巴脉管系统由较大的集合管和较小的毛细血管组成，具有促进细胞内渗的特殊细胞连接。通常，这些连接点旨在收集免疫细胞和其他细胞成分，以供淋巴结进行免疫监视，但癌细胞也利用它们来促进转移。尽管体内淋巴管的整体发育已经得到了很好的表征，但很少有人关注乳腺中的淋巴管网络在妊娠、哺乳和产后复旧等重塑阶段如何变化。在这篇综述中，我们的目的是定义目前已知的乳腺形态发生过程中的淋巴管生成因子和淋巴重塑事件。此外，我们将乳腺青春期发育和产后复旧并置，以显示促淋巴管生成信号以及在这些形态发生阶段至关重要的上皮细胞存活的其他分子信号的相似性。类似的机制包括 M2 极化巨噬细胞的参与，有助于基质重塑和血管生成；信号转导子和转录激活子 (STAT) 生存和增殖信号转导；环加氧酶 2 (COX2)/前列腺素 E2 (PGE2) 信号传导促进导管和淋巴管扩张。对正常乳腺中淋巴管生成的研究和表征可以深入了解乳腺癌中淋巴管生成和肿瘤细胞淋巴扩散的靶向机制。