Members of the Ren Lab have investigated the effects of a new pathway, the LPA/PKD-1 -CD36 signaling axis, on tumor angiogenesis and breast cancer stem cells, a subpopulation of breast cancer cells essential for tumor initiation, metastasis, and recurrence.
The Ren Lab has recently published “Development of an arteriolar niche and self-renewal of breast cancer stem cells by lysophosphatidic acid/protein kinase D signaling” in the Communications Biology (Springer Nature).
According to the article, they demonstrated the existence of an arteriolar niche in the tumor microenvironment (TME) of human estrogen receptor positive breast cancer tissues for the first time. Intriguingly, breast cancer stem cells tend to be accumulated within the arteriolar niche within the tumor microenvironment.
Moreover, breast cancer cells may bi-directionally interact with arteriolar endothelial cells, thereby promoting the development of stem-like features in the cancer cells. The interaction between breast cancer cells and arteriolar microenvironment (Niche) may be driven by the lysophosphatidic acid (LPA)/protein kinase D (PKD-1) signaling pathway, which promotes both arteriolar differentiation of vascular endothelial cells and self-renewal of cancer stem cells likely via differential regulation of CD36 transcription.
Their study indicates that CSCs may enjoy blood perfusion to maintain their stemness features. Targeting the LPA/PKD-1 -CD36 signaling pathway may have therapeutic potential to curb tumor progression by disrupting the arteriolar niche and effectively eliminating CSCs.
“If we want to disrupt the expansion of breast cancer stem cells, targeting the LPA/PKD-1 -CD36 signaling pathway may show great promise,” said Bin Ren, M.D., Ph.D., FAHA, the senior author of this study and the William D. Jordan, Jr. M.D., Endowed Professor in Vascular Sciences.
“This study reminds us of the importance of researchers honing in on the vascular microenvironment, in which aggressive cancer stem-like cells can stay for nutrients and oxygen, and get educated and equipped to endure and survive the harsh environment in the blood circulation,” said Ren. “The proof-of-principle by further research may generate huge impact on research in the tumor microenvironment and cancer stem cells. We are excited about this finding and look forward to continuing our investigations.”
“I am proud of the work of our lab,” said Ren. “Each of our lab members excels in their research and continues to press forward to understand underlying mechanisms of tumors progression and potentially find new ways to treat cancers. The collaboration between basic researchers and clinicians also contributes to the success of this initial work.”
Authors in this research include:
- Yinan Jiang, M.D., Ph.D.
- Yichen Guo, BS
- Jinjin Hao, M.D., Ph.D.
- Rachael Guenter, Ph.D.
- Justin Lathia, Ph.D.
- Adam W. Beck, M.D.
- Reagan Hattaway, BS
- Douglas Hurst, Ph.D.
- Qiming Jane Wang, Ph.D.
- Yehe Liu, Ph.D.
- Qi Cao, Ph.D., M.D.
- Helen Krontiras, M.D.
- Herbert Chen, M.D., FACS
- Roy Silverstein, M.D.
- Bin Ren, M.D., Ph.D., FAHA
To learn more about study methods and read the entire article, click here.