Author:
Jiang Yinan,Guo Yichen,Hao Jinjin,Guenter Rachael,Lathia Justin,Beck Adam,Hattaway Reagan,Hurst Doug,Wang Q Jane,Liu Yehe,Cao Qi,Krontiras Helen,Chen Herbert,Silverstein Roy,Ren Bin
Abstract
ABSTRACTBreast cancer stem cells (BCSCs) are essential for cancer growth, metastasis and recurrence. However, the regulatory mechanisms of self-renewal and interactions with the vascular niche within tumor microenvironment are currently under investigation. Here, we demonstrate that BCSCs are enriched within arteriolar niche within the tumor microenvironment of estrogen receptor positive (ER+) BC and bi-directionally interact with arteriolar endothelial cells (ECs). Mechanistically, this interaction is driven by the LPA/PKD-1 signaling pathway, which promotes arteriolar differentiation and self-renewal. Furthermore, this pathway directly promotes stemness features. These findings suggest that targeting LPA/PKD-1 signaling may disrupt the arteriolar niche within the tumor microenvironment and concomitantly eradicate BCSCs, thereby attenuating BC progression.
Publisher
Cold Spring Harbor Laboratory