Adipocyte-induced CD36 expression drives ovarian cancer progression and metastasis

Ladányi, András; Mukherjee, Abir; Kenny, Hilary A.; Johnson, Alyssa E.; Mitra, Anirban; Sundaresan, Sinju; Nieman, Kristin M.; Pascual, Gloria; Benitah, Salvador Aznar; Montag, Anthony; Yamada, S. Diane; Abumrad, Nada A.; Lengyel, Ernst

doi:10.1038/s41388-017-0093-z

Cited by 382 publications

(352 citation statements)

References 59 publications

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“…Recently, multiple studies have shown that cancer cells with increased expression of fatty acid receptor, CD36, are able to initiate metastasis and promote self‐renewal . It is particularly noteworthy that omental adipocytes are able to induce expression of CD36 in ovarian cancer .…”

Section: Obesity and Age‐related Diseasesmentioning

confidence: 88%

Obesity and ageing: Two sides of the same coin

2020

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Summary Conditions and comorbidities of obesity mirror those of ageing and age‐related diseases. Obesity and ageing share a similar spectrum of phenotypes such as compromised genomic integrity, impaired mitochondrial function, accumulation of intracellular macromolecules, weakened immunity, shifts in tissue and body composition, and enhanced systemic inflammation. Moreover, it has been shown that obesity reduces life expectancy by 5.8 years in men and 7.1 years in women after the age of 40. Shorter life expectancy could be because obesity holistically accelerates ageing at multiple levels. Besides jeopardizing nuclear DNA and mitochondrial DNA integrity, obesity modifies the DNA methylation pattern, which is associated with epigenetic ageing in different tissues. Additionally, other signs of ageing are seen in individuals with obesity including telomere shortening, systemic inflammation, and functional declines. This review aims to show how obesity and ageing are “two sides of the same coin” through discussing how obesity predisposes an individual to age‐related conditions, illness, and disease. We will further demonstrate how the mechanisms that perpetuate the early‐onset of chronic diseases in obesity parallel those of ageing.

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Section: Obesity and Age‐related Diseasesmentioning

confidence: 88%

Obesity and ageing: Two sides of the same coin

2020

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“…Glycolysis and oxidative phosphorylation were measured with the Seahorse Extracellular Flux XF-96) analyzer (Seahorse Bioscience, North Billerica, MA) (Ladanyi et al, 2018). Cells were seeded in Seahorse XF-96 plates at a density of 10,000 cells per well and cultured for 24hr.…”

Section: Star Methodsmentioning

confidence: 99%

Fibroblasts Mobilize Tumor Cell Glycogen to Promote Proliferation and Metastasis

et al. 2019

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Successful metastasis requires the co-evolution of stromal and cancer cells. We used stable isotope labeling of amino acids in cell culture coupled with quantitative, label-free phosphoproteomics to study the bidirectional signaling in ovarian cancer cells and human-derived, cancer-associated fibroblasts (CAFs) after co-culture. In cancer cells, the interaction with CAFs supported glycogenolysis under normoxic conditions and induced phosphorylation and activation of phosphoglucomutase 1, an enzyme involved in glycogen metabolism. Glycogen was funneled into glycolysis, leading to increased proliferation, invasion, and metastasis of cancer cells co-cultured with human CAFs. Glycogen mobilization in cancer cells was dependent on p38α MAPK activation in CAFs. In vivo, deletion of p38α in CAFs and glycogen phosphorylase inhibition in cancer cells reduced metastasis, suggesting that glycogen is an energy source used by cancer cells to facilitate metastatic tumor growth.

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“…) or adipocytes (Ladanyi et al. ). We propose an additional role for sympathetic innervation of OMSs.…”

Section: Discussionmentioning

confidence: 99%

Sympathetic nerve tissue in milky spots of the human greater omentum

et al. 2019

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Omental milky spots (OMSs), small lymphoid structures positioned in the greater omentum, are involved in peritoneal immune homeostasis and the formation of omental metastases. Sympathetic nerve activity is known to regulate immune function in other lymphoid organs (e.g. spleen and lymph nodes) and to create a favourable microenvironment for various tumour types. However, it is still unknown whether OMSs receive sympathetic innervation. Therefore, the aim of this study was to establish whether OMSs of the adult human greater omentum receive sympathetic innervation. A total of 18 OMSs were isolated from five omenta, which were removed from 3% formaldehyde‐perfused cadavers (with a median age of 84 years, ranging from 64 to 94). OMSs were embedded in paraffin, cut and stained with a general (PGP9.5) and sympathetic nerve marker (TH and DBH), and evaluated by bright field microscopy. A T‐cell, B‐cell, and macrophage staining was performed to confirm OMS identity. In 50% of the studied OMSs, sympathetic nerve fibres were observed at multiple levels of the same OMS. Nerve fibres were represented as dots or elongated structures and often observed in relation to small vessels and occasionally as individual structures residing between lymphoid cells. The current study shows that 50% of the investigated OMSs contain sympathetic nerve fibres. These findings may contribute to our understanding of neural regulation of peritoneal immune response and the involvement of OMSs in omental metastases.

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Adipocyte-induced CD36 expression drives ovarian cancer progression and metastasis

Cited by 382 publications

References 59 publications

Obesity and ageing: Two sides of the same coin

Obesity and ageing: Two sides of the same coin

Fibroblasts Mobilize Tumor Cell Glycogen to Promote Proliferation and Metastasis

Sympathetic nerve tissue in milky spots of the human greater omentum

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