Composition and turnover of phospholipids and neutral lipids in human breast cancer and reference tissues

Sakai, Keiko; Okuyama, Harumi; Yura, Jiro; Takeyama, Hidemaro; Shinagawa, N; Tsuruga, Nobuatsu; Kato, Koichi; Miura, K; Kawase, Kumiko; Tsujimura, Takahiro

doi:10.1093/carcin/13.4.579

Cited by 73 publications

(51 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies indicate that the phospholipid content is 4-fold higher and the triacylglycerol content is 65% lower in cancer compared with noncancerous parts of the breast tissue (40). Moreover, the fatty acid composition of the cancer tissue phospholipids was highly enriched in unsaturated FFAs compared with noncancerous tissue, whereas triacylglycerol revealed no significant difference between cancer and normal tissue (40). Consistent with these observations, cis unsaturated FFAs are the predominant FFAs released from breast cancer tissue (Fig.…”

Section: Discussionsupporting

confidence: 82%

“…Microscopic examination of dispersions of cells from selected breast tumor samples did not reveal significant amounts of intracellular lipid droplets (data not shown). Previous studies indicate that the phospholipid content is 4-fold higher and the triacylglycerol content is 65% lower in cancer compared with noncancerous parts of the breast tissue (40). Moreover, the fatty acid composition of the cancer tissue phospholipids was highly enriched in unsaturated FFAs compared with noncancerous tissue, whereas triacylglycerol revealed no significant difference between cancer and normal tissue (40).…”

Section: Discussionmentioning

confidence: 87%

See 1 more Smart Citation

Free fatty acid release from human breast cancer tissue inhibits cytotoxic T-lymphocyte-mediated killing

Kleinfeld

Okada

2005

Journal of Lipid Research

View full text Add to dashboard Cite

Immune-mediated antitumor activities confront a variety of tumor-mediated defense mechanisms. Here, we describe a new mechanism involving FFA that may allow breast cancer to evade immune clearance. We determined the IC 50 at which unbound free fatty acids (FFA u ) inhibit murine cytotoxic T-lymphocyte (CTL)-mediated killing to assess the physiologic relevance of this phenomenon. We found that the IC 50 for unbound oleate is 125 ؎ 30 nM, ‫ف‬ 200-fold greater than normal plasma levels. FFA inhibition, however, may play an important role in breast cancer because we found that large quantities of FFAs are released constitutively into the media surrounding samples of human breast cancer but not normal or benign tissue. Antitumor cytotoxic T-lymphocytes (CTLs) are central to immunotherapeutic anticancer strategies (1-5). Tumorspecific CTLs can be induced by various immunotherapeutic strategies (reviewed in 3), and tumor-infiltrating lymphocytes are found "naturally" in tumors (6). Nevertheless, immunotherapeutic methods are rarely effective in mediating the regression or clearance of established tumors. This lack of effectiveness suggests that factors other than CTL activation may prevent CTL-mediated clearance of tumor in vivo. A number of factors have been identified that reduce CTL effectiveness, including loss of tumor antigen, major histocompatibility complex class I downregulation, and a physical barrier separating CTL and tumor (3). In the present study, we provide evidence for a new mechanism: inhibition of CTL killing of tumor cells by FFAs produced by human breast cancer tumors.Inhibition of CTL activity by increased levels of total FFAs has been demonstrated in several in vitro studies (7-16). Increased levels of cis unsaturated FFAs inhibit CTL signaling pathways and, in particular, inhibit CTLmediated killing of cognate target cells. These inhibitory effects of cis FFAs are attributable to an immediate physical perturbation of the CTL; the effects occur within seconds and are reversed upon extracting FFAs with extracellular albumin. In contrast, saturated FFAs have no effect on signaling or killing. The differential effects of cis and saturated FFAs does not involve FFA metabolism because CTL inhibition can be detected before metabolite levels are significant and because the predominant metabolites of oleic acid (the most potent FFA inhibitor) cannot be extracted with extracellular albumin (9). The differential effects of cis and saturated FFAs, however, are well correlated with differential effects of cis and saturated FFAs on membrane lipid order (10,14), consistent with a physical mechanism of FFA-mediated CTL inhibition.In biological fluids, most FFA is bound to albumin and/ or cells (17,18). Although only a small fraction of total FFA is unbound free fatty acids (FFA u ) (19), it is the FFA u that determine the degree of FFA inhibition of cellular function (14). FFA u levels that inhibit CTL-mediated killing have not been determined. Estimates have been obtained for FFA u levels (IC 50 ) tha...

show abstract

Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 87%

Free fatty acid release from human breast cancer tissue inhibits cytotoxic T-lymphocyte-mediated killing

Kleinfeld

Okada

2005

Journal of Lipid Research

View full text Add to dashboard Cite

show abstract

“…Among the highly significant peaks identified were several fatty acids (FA), phosphatidylethanolamines (PE), phosphatidylcholines (PC) and phosphatidylinositols (PI). Fold changes between 2 and 14 were observed (mean fold change ¼ 5), which is close to fold changes reported in the literature (30,31). Only a small number of peaks with medium significance for tissue separation were found in greater abundance in the morphologically normal glandular tissue.…”

Section: Tissue-specific Metabolomic Profilingsupporting

confidence: 87%

“…The most intense peaks, with a P value < 2 Â 10 À5 , are summarized in Table 3. Very high fold changes (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37) were found for signals associated with lactate and calcidiol. Lactate was found as a dimer and in form of several sodium chloride clusters (MþNa 4 Cl 4 , MþNa 3 Cl 3 , MþNa 2 Cl 2 ).…”

Section: Tissue-specific Metabolomic Profilingmentioning

confidence: 99%

Spatially Resolved Metabolic Phenotyping of Breast Cancer by Desorption Electrospray Ionization Mass Spectrometry

et al. 2015

View full text Add to dashboard Cite

Breast cancer is a heterogeneous disease characterized by varying responses to therapeutic agents and significant differences in long-term survival. Thus, there remains an unmet need for early diagnostic and prognostic tools and improved histologic characterization for more accurate disease stratification and personalized therapeutic intervention. This study evaluated a comprehensive metabolic phenotyping method in breast cancer tissue that uses desorption electrospray ionization mass spectrometry imaging (DESI MSI), both as a novel diagnostic tool and as a method to further characterize metabolic changes in breast cancer tissue and the tumor microenvironment. In this prospective single-center study, 126 intraoperative tissue biopsies from tumor and tumor bed from 50 patients undergoing surgical resections were subject to DESI MSI. Global DESI MSI models were able to distinguish adipose, stromal, and glandular tissue based on their metabolomic fingerprint. Tumor tissue and tumor-associated stroma showed evident changes in their fatty acid and phospholipid composition compared with normal glandular and stromal tissue. Diagnosis of breast cancer was achieved with an accuracy of 98.2% based on DESI MSI data (PPV 0.96, NVP 1, specificity 0.96, sensitivity 1). In the tumor group, correlation between metabolomic profile and tumor grade/hormone receptor status was found. Overall classification accuracy was 87.7% (PPV 0.92, NPV 0.9, specificity 0.9, sensitivity 0.92). These results demonstrate that DESI MSI may be a valuable tool in the improved diagnosis of breast cancer in the future. The identified tumor-associated metabolic changes support theories of de novo lipogenesis in tumor tissue and the role of stroma tissue in tumor growth and development and overall disease prognosis. Cancer Res; 75(9); 1828-37. Ó2015 AACR.

show abstract

“…The most widely recognized role of lipids is to form the lipid bilayer of cellular and organelle membranes [8]. It has been reported that alterations in the glycerophospholipid composition of tissues occur in several diseases, including cancer [9] and Alzheimer's disease [10]. Particular glycerophospholipids and their enzymatic products have been identified in malignant transformations in tissue [11,12].…”

mentioning

confidence: 99%

Desorption electrospray ionization imaging mass spectrometry of lipids in rat spinal cord

Girod

Shi

Cheng

et al. 2010

J. Am. Soc. Mass Spectrom.

View full text Add to dashboard Cite

Imaging mass spectrometry allows for the direct investigation of tissue samples to identify specific biological compounds and determine their spatial distributions. Desorption electrospray ionization (DESI) mass spectrometry has been used for the imaging and analysis of rat spinal cord cross sections. Glycerophospholipids and sphingolipids, as well as fatty acids, were detected in both the negative and positive ion modes and identified through tandem mass spectrometry (MS/MS) product ion scans using collision-induced dissociation and accurate mass measurements. Differences in the relative abundances of lipids and free fatty acids were present between white and gray matter areas in both the negative and positive ion modes. DESI-MS images of the corresponding ions allow the determination of their spatial distributions within a cross section of the rat spinal cord, by scanning the DESI probe across the entire sample surface. Glycerophospholipids and sphingolipids were mostly detected in the white matter, while the free fatty acids were present in the gray matter. These results show parallels with reported distributions of lipids in studies of rat brain. This suggests that the spatial intensity distribution reflects relative concentration differences of the lipid and fatty acid compounds in the spinal cord tissue. The "butterfly" shape of the gray matter in the spinal cord cross section was resolved in the corresponding ion images, indicating that a lateral resolution of better than 200 m was achieved. The selected ion images of lipids are directly correlated with anatomic features on the spinal cord corresponding to the white and the gray

show abstract

Composition and turnover of phospholipids and neutral lipids in human breast cancer and reference tissues

Cited by 73 publications

References 0 publications

Free fatty acid release from human breast cancer tissue inhibits cytotoxic T-lymphocyte-mediated killing

Free fatty acid release from human breast cancer tissue inhibits cytotoxic T-lymphocyte-mediated killing

Spatially Resolved Metabolic Phenotyping of Breast Cancer by Desorption Electrospray Ionization Mass Spectrometry

Desorption electrospray ionization imaging mass spectrometry of lipids in rat spinal cord

Contact Info

Product

Resources

About