Search bioRxivSearch

Biology subjects

Jones, J. G.

Publications and source records attributed to Jones, J. G..

2 recordsLinked to original sources

Positional and Compositional Analysis of Saturated, Monounsaturated and Polyunsaturated Fatty acids in Human Adipose Tissue Triglyceride by 13C NMR

Objectives and new findings, ends with short conclusion, no referencesThe synthesis and turnover of triglyceride in adipose tissue involves enzymes with preferences for specific fatty acid classes and/or regioselectivity with regard to the fatty acid position within the glycerol moiety. The focus of the present study was to characterize both the fatty acid composition and their positional distribution in triglycerides of biopsied human subcutaneous adipose tissue using 13C NMR spectroscopy. The triglyceride sn2 position was significantly more enriched with monounsaturated fatty acids compared to the sn1,3 sites, while saturated fatty acids abundance was significantly lower in the sn2 position compared to that of sn1,3. Furthermore, the analysis revealed significant positive correlations between the total fraction of palmitoleic acid with both BMI and HOMA-IR scores. Additionally, we established that 13C NMR chemical shifts for {omega} -3 signals, centered at 31.9 ppm, provided superior resolution of the most abundant FA species, including palmitoleate, compared to the {omega} -2 signals that were used previously. 13C NMR spectroscopy reveals for the first time a highly non-homogenous distribution of FA in the glycerol sites of human adipose tissue triglyceride and that these distributions are correlated with different phenotypes such as BMI and insulin resistance.

biochemistry

Live imaging of breast tumors shows macrophage-dependent induction and TMEM-mediated enrichment of cancer stem cells during metastatic dissemination

Cancer stem cells (CSCs) play an important role during metastasis, but the dynamic behavior and induction mechanisms of CSCs are not well understood. We employed high-resolution intravital microscopy using a CSC biosensor to directly observe CSCs in live mice with mammary tumors. CSCs display the slow-migratory, invadopod-rich phenotype that is the hallmark of disseminating tumor cells. CSCs are enriched near macrophages, particularly near macrophage-containing intravasation sites called Tumor Microenvironment of Metastasis (TMEM) doorways. A dramatic enrichment of CSCs occurs on association with TMEM doorways, contributing to the finding that CSCs represent [~]>60% of circulating tumor cells. Mechanistically, stemness is induced in non-stem cancer cells upon their direct contact with macrophages via Notch signaling. In breast cancers from patients, the density of TMEM doorways correlates strongly with the proportion of cancer cells expressing stem cell markers, indicating that in human breast cancer TMEM doorways are not only cancer cell intravasation portals but also CSC programming sites. One Sentence SummaryIntravital imaging reveals macrophage-mediated induction of cancer stem cells in vivo and their dramatic enrichment on dissemination through TMEM doorways.

cancer biology