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Citations to this article

Cyclooxygenase-2–dependent lymphangiogenesis promotes nodal metastasis of postpartum breast cancer
Traci R. Lyons, … , Sonali Jindal, Pepper Schedin
Traci R. Lyons, … , Sonali Jindal, Pepper Schedin
Published August 18, 2014
Citation Information: J Clin Invest. 2014;124(9):3901-3912. https://doi.org/10.1172/JCI73777.
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Cyclooxygenase-2–dependent lymphangiogenesis promotes nodal metastasis of postpartum breast cancer

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Abstract

Breast involution following pregnancy has been implicated in the high rates of metastasis observed in postpartum breast cancers; however, it is not clear how this remodeling process promotes metastasis. Here, we demonstrate that human postpartum breast cancers have increased peritumor lymphatic vessel density that correlates with increased frequency of lymph node metastases. Moreover, lymphatic vessel density was increased in normal postpartum breast tissue compared with tissue from nulliparous women. In rodents, mammary lymphangiogenesis was upregulated during weaning-induced mammary gland involution. Furthermore, breast cancer cells exposed to the involuting mammary microenvironment acquired prolymphangiogenic properties that contributed to peritumor lymphatic expansion, tumor size, invasion, and distant metastases. Finally, in rodent models of postpartum breast cancer, cyclooxygenase-2 (COX-2) inhibition during the involution window decreased normal mammary gland lymphangiogenesis, mammary tumor-associated lymphangiogenesis, tumor cell invasion into lymphatics, and metastasis. Our data indicate that physiologic COX-2–dependent lymphangiogenesis occurs in the postpartum mammary gland and suggest that tumors within this mammary microenvironment acquire enhanced prolymphangiogenic activity. Further, our results suggest that the prolymphangiogenic microenvironment of the postpartum mammary gland has potential as a target to inhibit metastasis and suggest that further study of the therapeutic efficacy of COX-2 inhibitors in postpartum breast cancer is warranted.

Authors

Traci R. Lyons, Virginia F. Borges, Courtney B. Betts, Qiuchen Guo, Puja Kapoor, Holly A. Martinson, Sonali Jindal, Pepper Schedin

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Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2009 Total
Citations: 4 11 9 9 7 10 6 10 6 7 4 2 1 86
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