S1P Promotes Breast Cancer Progression by Angiogenesis and Lymphangiogenesis

Mukhopadhyay, Partha; Ramanathan, R. K.; Takabe, Kazuaki

doi:10.2217/bmt.15.20

Cited by 20 publications

(24 citation statements)

References 20 publications

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“…Sphingolipids such as S1P and ceramides are known to have regulatory roles in controlling tumor proliferation, migration, and angiogenesis [ 15 , 16 , 25 ]. While ceramides and S1P have traditionally been assigned opposing roles in promoting and inhibiting apoptosis in cancer cells, respectively, it is now recognized that the role of ceramides in cancer progression is much more complex [ 17 , 33 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

“…Increased ceramide production by cancer cells following chemotherapy treatment has been shown to induce apoptosis and ceramide analogs have themselves shown promise as potential cancer treatments [ 22 , 23 ]. S1P production by cancer cells also simulates angiogenesis through lipid signaling to the tumor microenvironment [ 24 , 25 ]. It has also been shown that sphingoid bases such as sphinganine and sphingosine, which serve as metabolic intermediates in the synthesis of ceramide and S1P, can also induce apoptosis in cancer cells [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

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Unbiased Lipidomic Profiling of Triple-Negative Breast Cancer Tissues Reveals the Association of Sphingomyelin Levels with Patient Disease-Free Survival

Purwaha

Piyarathna

et al. 2018

Metabolites

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The reprogramming of lipid metabolism is a hallmark of many cancers that has been shown to promote breast cancer progression. While several lipid signatures associated with breast cancer aggressiveness have been identified, a comprehensive lipidomic analysis specifically targeting the triple-negative subtype of breast cancer (TNBC) may be required to identify novel biomarkers and therapeutic targets for this most aggressive subtype of breast cancer that still lacks effective therapies. In this current study, our global LC-MS-based lipidomics platform was able to measure 684 named lipids across 15 lipid classes in 70 TNBC tumors. Multivariate survival analysis found that higher levels of sphingomyelins were significantly associated with better disease-free survival in TNBC patients. Furthermore, analysis of publicly available gene expression datasets identified that decreased production of ceramides and increased accumulation of sphingoid base intermediates by metabolic enzymes were associated with better survival outcomes in TNBC patients. Our LC-MS lipidomics profiling of TNBC tumors has, for the first time, identified sphingomyelins as a potential prognostic marker and implicated enzymes involved in sphingolipid metabolism as candidate therapeutic targets that warrant further investigation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Unbiased Lipidomic Profiling of Triple-Negative Breast Cancer Tissues Reveals the Association of Sphingomyelin Levels with Patient Disease-Free Survival

Purwaha

Piyarathna

et al. 2018

Metabolites

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“…The function of S1P is go through its receptors S1PRs (S1PR1‐5) which belongs to the G‐protein coupled receptor (GPCR) family 2 and each receptor, respectively, involved in cell growth, apoptosis, proliferation, angiogenesis, chemo resistance, or vascular stability 5, 13, 14, 15. It is also a chemotactic factor for immune cell trafficking 5, 16, 17 and a microenvironmental regulator for cancer development 18. The growth rate of breast cancer cells was found to be decreased in SPHK1 or SPHK2 deficient mice 19.…”

Section: Introductionmentioning

confidence: 99%

Survival benefit of sphingosin‐1‐phosphate and receptors expressions in breast cancer patients

Cheng

Liao

et al. 2018

Cancer Medicine

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Sphingosine‐1‐phosphate (S1P) is a bioactive lipid that exerts various pathophysiological functions through binding to its receptor family (S1PRs). Since first report of the breast cancer (BCA) promoting function by S1P production (through the function of sphingosine kinases) and S1P/S1PR signaling, their antagonists have never been successfully progress to clinics after three decades. Taking advantage of bioinformatics linking to gene expression to disease prognosis, we examined the impact of associated genes in BCA patients. We found high gene expressions involved in S1P anabolism suppressed disease progression of patients who are basal cell type BCA or receiving adjuvant therapy. In addition, S1PRs expression also suppressed disease progress of multiple categories of BCA patient progression. This result is contradictory to tumor promoter role of S1P/S1PRs which revealed in the literature. Further examination by directly adding S1P in BCA cells found a cell growth suppression function, which act via the expression of S1PR1. In conclusion, our study is the first evidence claiming a survival benefit function of S1P/S1PR signaling in BCA patients, which might explain the obstacle of relative antagonist apply in clinics.

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“…S1P exerts its actions in cell survival migration and angiogenesis, thereby affecting cancer progression in several solid tumors [8]. We have reported that secreted S1P generates lymphatic vessels in tumor microenvironment [11, 12] and that is associated with increased lymph node metastasis in breast cancer patients [11, 14].…”

Section: Discussionmentioning

confidence: 99%

Paradoxical Association of Postoperative Plasma Sphingosine-1-Phosphate with Breast Cancer Aggressiveness and Chemotherapy

Ramanathan

Ali

Sturgill

et al. 2017

Mediators of Inflammation

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Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator that has been shown to serve an important regulatory function in breast cancer progression. This study analyzes plasma S1P levels in breast cancer patients undergoing adjuvant therapy as compared to healthy control volunteers. 452 plasma S1P samples among 158 breast cancer patients, along with 20 healthy control volunteers, were analyzed. Mean S1P levels did not significantly differ between cancer patients and controls. Smoking was associated with higher S1P levels in cancer patients. Baseline S1P levels had weak inverse correlation with levels of the inflammatory mediator interleukin- (IL-) 17 and CCL-2 and positive correlation with tumor necrosis factor alpha (TNF-α). Midpoint S1P levels during adjuvant therapy were lower than baseline, with near return to baseline after completion, indicating a relationship between chemotherapy and circulating S1P. While stage of disease did not correlate with plasma S1P levels, they were lower among patients with Her2-enriched and triple-negative breast cancer as compared to luminal-type breast cancer. Plasma S1P levels are paradoxically suppressed in aggressive breast cancer and during adjuvant chemotherapy, which raises the possibility that postoperative plasma S1P levels do not reflect S1P secretion from resected breast cancer.

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S1P Promotes Breast Cancer Progression by Angiogenesis and Lymphangiogenesis

Cited by 20 publications

References 20 publications

Unbiased Lipidomic Profiling of Triple-Negative Breast Cancer Tissues Reveals the Association of Sphingomyelin Levels with Patient Disease-Free Survival

Unbiased Lipidomic Profiling of Triple-Negative Breast Cancer Tissues Reveals the Association of Sphingomyelin Levels with Patient Disease-Free Survival

Survival benefit of sphingosin‐1‐phosphate and receptors expressions in breast cancer patients

Paradoxical Association of Postoperative Plasma Sphingosine-1-Phosphate with Breast Cancer Aggressiveness and Chemotherapy

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