American Association for Cancer Research
15417786mcr140188-sup-129639_1_supp_2529851_n7kwnp.pptx (606.63 kB)

Data Supplement from Bioactive Lipids, LPC and LPA, Are Novel Prometastatic Factors and Their Tissue Levels Increase in Response to Radio/Chemotherapy

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posted on 2023-04-03, 16:26 authored by Gabriela Schneider, Zachariah Payne Sellers, Ahmed Abdel-Latif, Andrew J. Morris, Mariusz Z. Ratajczak

Supplementary Figure 1. Wound healing assay indicates that LPA and LPC may induce chemokinesis of RMS cells. Panel A - Representative pictures taken during wound healing assay. Panel B - Statistical analysis of number of cells that migrate into wound.



Bioactive lipids are fundamental mediators of a number of critical biologic processes such as inflammation, proliferation, and apoptosis. Rhabdomyosarcoma (RMS) is common in adolescence with histologic subtypes that favor metastasis. However, the factors that influence metastasis are not well appreciated. Here, it is shown that lysophosphatidylcholine (LPC) and its derivative, lysophosphatidic acid (LPA), strongly enhance motility and adhesion of human RMS cells. Importantly, these metastatic-associated phenotypes were observed at physiologic concentrations of these lipids, which naturally occur in biologic fluids. Moreover, the effects of these bioactive lipids were much stronger as compared with known peptide-based prometastatic factors in RMS, such as stromal-derived factor-1 or hepatocyte growth factor/scatter factor. Finally, both LPC and LPA levels were increased in several organs after γ-irradiation or chemotherapy, supporting the hypothesis that radio/chemotherapy induces an unwanted prometastatic environment in these organs.Implications: LPC and LPA play a previously underappreciated role in dissemination of RMS and suggest that antimetastatic treatment with specific molecules blocking LPC/LPA activity should be part of standard radio/chemotherapy arsenal. Mol Cancer Res; 12(11); 1560–73. ©2014 AACR.