American Association for Cancer Research
15417786mcr140188-sup-129639_1_supp_2529853_n7kxrp.pptx (265.21 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 3. Ki16425 is not toxic against RMS cells. Panel A - Proliferation of RH30 cells pretreated for 1h with 10 μM or 50 μM Ki15425 in comparison to control cells pretreated with vehicle only. Panel B - Representative FACS analysis of Anexin V binding and propidium iodide incorporation into RMS cells 24h after pre-treatment with Ki16425. Panel C - Analysis of Anexin V and propidium iodide staining in cells 24h and 48h after 1h pre-treatment pre with Ki16425. Pre-treatment was done in PBS, then cells were washed out from inhibitor, resuspended in medium supplemented with 10% FBS and cultured in suspension in low cell adherence dishes. Panel D - Analysis of Anexin V and propidium iodide staining in RMS cells exposed for 48 hours to Ki16425. Cells were incubated in the presence of inhibitor in medium supplemented with 0.5% BSA or 10% FBS.



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.