Dipalmitoylphosphatidic acid inhibits breast cancer growth by suppressing angiogenesis via inhibition of the CUX1/FGF1/HGF signalling pathway.

Abstract

Tumour growth depends on a continual supply of the nutrients and oxygen, which are offered by tumour angiogenesis. Our previous study showed that dipalmitoylphosphatidic acid (DPPA), a bioactive phospholipid, inhibits the growth of triple-negative breast cancer cells. However, its direct effect on angiogenesis remains unknown. Our work showed that DPPA significantly suppressed vascular growth in the chick embryo chorioallantoic membrane (CAM) and yolk sac membrane (YSM) models. Meanwhile, tumour angiogenesis and tumour growth were inhibited by DPPA in the tumour tissues of an experimental breast cancer model, a subcutaneous xenograft mouse model and a genetically engineered spontaneous breast cancer mouse model (MMTV-PyMT). Furthermore, DPPA directly inhibited the proliferation, migration and tube formation of vascular endothelial cells. The anti-angiogenic effect of DPPA was regulated by the inhibition of Cut-like homeobox1 (CUX1), which transcriptionally inhibited fibroblast growth factor 1 (FGF1), leading to the downregulation of hepatocyte growth factor (HGF). This work first demonstrates that DPPA directly inhibits angiogenesis in cancer development. Our previous work along with this study suggest that DPPA functions as an anti-tumour therapeutic drug that inhibits angiogenesis.

• Authors: Jian Chen, Zijun Zhou, Yuying Yao, Jianwei Dai, Dalei Zhou, Lijing Wang, Qian-Qian Zhang
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 22 Issue 10 Pg. 4760-4770 (10 2018) ISSN: 1582-4934 [Electronic] England
• PMID: 30010249 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Chemical References

• Antineoplastic Agents
• CUX1 protein, human
• Homeodomain Proteins
• Nuclear Proteins
• Phosphatidic Acids
• Repressor Proteins
• Transcription Factors
• Fibroblast Growth Factor 1
• dipalmitoylphosphatidic acid
• Hepatocyte Growth Factor

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Chick Embryo
• Chorioallantoic Membrane (blood supply, drug effects)
• Female
• Fibroblast Growth Factor 1 (genetics, metabolism)
• Gene Expression Regulation, Neoplastic
• Hepatocyte Growth Factor (genetics, metabolism)
• Homeodomain Proteins (genetics, metabolism)
• Human Umbilical Vein Endothelial Cells (cytology, drug effects, metabolism)
• Humans
• Mammary Neoplasms, Experimental (drug therapy, genetics, metabolism, pathology)
• Mice
• Mice, Nude
• Neovascularization, Pathologic (genetics, metabolism, pathology, prevention & control)
• Nuclear Proteins (genetics, metabolism)
• Phosphatidic Acids (pharmacology)
• Repressor Proteins (genetics, metabolism)
• Signal Transduction (drug effects)
• Transcription Factors
• Triple Negative Breast Neoplasms (drug therapy, genetics, metabolism, pathology)
• Tumor Burden (drug effects)
• Xenograft Model Antitumor Assays