bims-stacyt Biomed News
on Metabolism and the paracrine crosstalk between cancer and the organism
Issue of 2019–08–25
five papers selected by
Cristina Muñoz Pinedo, L’Institut d’Investigació Biomèdica de Bellvitge
  1. Glucose Restriction Plus Refeeding in Vitro Induce Changes of the Human Adipocyte Secretome with an Impact on Complement Factors and Cathepsins.
  2. Autophagy, cancer and angiogenesis: where is the link?
  3. Hypoxia Rapidly Induces the Expression of Cardiomyogenic Factors in Human Adipose-Derived Adherent Stromal Cells.
  4. TNF-α in Combination with Palmitate Enhances IL-8 Production via The MyD88- Independent TLR4 Signaling Pathway: Potential Relevance to Metabolic Inflammation.
  5. Short-term hypoxia promotes vascularization in co-culture system consisting of primary human osteoblasts and outgrowth endothelial cells.
  1. Int J Mol Sci. 2019 Aug 20. pii: E4055. [Epub ahead of print]20(16):
    Glucose Restriction Plus Refeeding in Vitro Induce Changes of the Human Adipocyte Secretome with an Impact on Complement Factors and Cathepsins.
    Qi Qiao, Freek G Bouwman, Marleen A van Baak, Johan Renes, Edwin C M Mariman.
      Adipose tissue is a major endocrine organ capable of secreting adipokines with a role in whole-body metabolism. Changes in the secretome profile during the development of obesity is suspected to contribute to the risk of health complications such as those associated with weight regain after weight loss. However, the number of studies on weight regain is limited and secretome changes during weight regain have hardly been investigated. In an attempt to generate leads for in vivo studies, we have subjected human Simpson Golabi Behmel Syndrome adipocytes to glucose restriction (GR) followed by refeeding (RF) as an in vitro surrogate for weight regain after weight loss. Using LC-MS/MS, we compared the secreted protein profile after GR plus RF with that of normal feeding (NF) to assess the consequences of GR plus RF. We identified 338 secreted proteins of which 49 were described for the first time as being secreted by adipocytes. In addition, comparison between NF and GR plus RF showed 39 differentially secreted proteins. Functional classification revealed GR plus RF-induced changes of enzymes for extracellular matrix modification, complement system factors, cathepsins, and several proteins related to Alzheimer's disease. These observations can be used as clues to investigate metabolic consequences of weight regain, weight cycling or intermittent fasting.
    Keywords:  SGBS adipocytes; adipokines; cathepsins; complement factors; extracellular remodeling; glucose restriction; in vitro fat regain; weight regain
    DOI:  https://doi.org/10.3390/ijms20164055
  2. Cell Biosci. 2019 ;9 65
    Autophagy, cancer and angiogenesis: where is the link?
    Bahareh Kardideh, Zahra Samimi, Fatemeh Norooznezhad, Sarah Kiani, Kamran Mansouri.
       Background: Autophagy is a catabolic process for degradation of intracellular components. Damaged proteins and organelles are engulfed in double-membrane vesicles ultimately fused with lysosomes. These vesicles, known as phagophores, develop to form autophagosomes. Encapsulated components are degraded after autophagosomes and lysosomes are fused. Autophagy clears denatured proteins and damaged organelles to produce macromolecules further reused by cells. This process is vital to cell homeostasis under both physiologic and pathologic conditions.
    Main body: While the role of autophagy in cancer is quite controversial, the majority of studies introduce it as an anti-tumorigenesis mechanism. There are evidences confirming this role of autophagy in cancer. Mutations and monoallelic deletions have been demonstrated in autophagy-related genes correlating with cancer promotion. Another pathway through which autophagy suppresses tumorigenesis is cell cycle. On the other hand, under hypoxia and starvation condition, tumors use angiogenesis to provide nutrients. Also, autophagy flux is highlighted in vessel cell biology and vasoactive substances secretion from endothelial cells. The matrix proteoglycans such as Decorin and Perlecan could also interfere with angiogenesis and autophagy signaling pathway in endothelial cells (ECs). It seems that the connection between autophagy and angiogenesis in the tumor microenvironment is very important in determining the fate of cancer cells.
    Conclusion: Matrix glycoproteins can regulate autophagy and angiogenesis linkage in tumor microenvironment. Also, finding details of how autophagy and angiogenesis correlate in cancer will help adopt more effective therapeutic approaches.
    Keywords:  Angiogenesis; Autophagy; Vessel cell biology
    DOI:  https://doi.org/10.1186/s13578-019-0327-6
  3. J Clin Med. 2019 Aug 15. pii: E1231. [Epub ahead of print]8(8):
    Hypoxia Rapidly Induces the Expression of Cardiomyogenic Factors in Human Adipose-Derived Adherent Stromal Cells.
    Jung-Won Choi, Hanbyeol Moon, Seung Eun Jung, Soyeon Lim, Seahyoung Lee, Il-Kwon Kim, Hoon-Bum Lee, Jiyun Lee, Byeong-Wook Song, Sang Woo Kim, Ki-Chul Hwang.
       BACKGROUND: The efficacy of interstitial vascular fraction (SVF) transplantation in the treatment of heart disease has been proven in a variety of in vivo studies. In a previous study, we found that bone marrow-derived mesenchymal stem cells (BM-MSCs) altered their expression of several cardiomyogenic factors under hypoxic conditions.
    METHODS: We hypothesized that hypoxia may also induce obtained adipose-derived adherent stromal cells (ADASs) from SVFs and adipose-derived stem cells (ASCs) to differentiate into cardiomyocytes and/or cells with comparable phenotypes. We examined the differentiation markers of cell lineages in ADASs and ASCs according to time by hypoxic stress and found that only ADASs expressed cardiomyogenic markers within 24 h under hypoxic conditions in association with the expression of hypoxia-inducible factor 1-α (HIF-1α).
    RESULTS: Differentially secreted proteins in a conditioned medium (CM) from ASCs and ADASs under normoxic or hypoxic conditions were detected using an antibody assay and may be associated with a dramatic increase in the expression of cardiomyogenic markers in only ADASs. Furthermore, the cardiomyogenic factors were expressed more rapidly in ADASs than in ASCs under hypoxic conditions in association with the expression of HIF-1α, and angiogenin, fibroblast growth factor-19 (FGF-19) and/or macrophage inhibitory factor (MIF) are related.
    CONCLUSIONS: These results provide new insights into the applicability of ADASs preconditioned by hypoxic stress in cardiac diseases.
    Keywords:  adipose-derived adherent stromal cells (ADASs); adipose-derived stem cells (ASCs); cardiomyocyte differentiation; hypoxia; stromal vascular fraction (SVF)
    DOI:  https://doi.org/10.3390/jcm8081231
  4. Int J Mol Sci. 2019 Aug 23. pii: E4112. [Epub ahead of print]20(17):
    TNF-α in Combination with Palmitate Enhances IL-8 Production via The MyD88- Independent TLR4 Signaling Pathway: Potential Relevance to Metabolic Inflammation.
    Amal Hasan, Nadeem Akhter, Areej Al-Roub, Reeby Thomas, Shihab Kochumon, Ajit Wilson, Merin Koshy, Ebaa Al-Ozairi, Fahd Al-Mulla, Rasheed Ahmad.
      Elevated levels of IL-8 (CXCL8) in obesity have been linked with insulin resistance and type 2 diabetes (T2D). The mechanisms that lead to the profound production of IL-8 in obesity remains to be understood. TNF-α and saturated free fatty acids (FFAs) are increased in obese humans and correlate with insulin resistance. Hence, we sought to investigate whether the cooccurrence of TNF-α and FFAs led to increase the production of IL-8 by human monocytes. We found that co-stimulation of human monocytes with palmitate and TNF-α led to increased IL-8 production as compared to those stimulated with palmitate or TNF-α alone. The synergistic production of IL-8 by TNF-α/palmitate was suppressed by neutralizing anti- Toll like receptor 4 (TLR4) antibody and by genetic silencing of TLR4. Both MyD88-deficient and MyD88-competent cells responded comparably to TNF-α/Palmitate. However, TIR-domain-containing adapter-inducing interferon (TRIF) inhibition or interferon regulatory transcription factor 3 (IRF3) knockdown partly blocked the synergistic production of IL-8. Our human data show that increased adipose tissue TNF-α expression correlated positively with IL-8 expression (r = 0.49, P = 0.001). IL-8 and TNF-α correlated positively with macrophage markers including CD68, CD163 and CD86 in adipose tissue. These findings suggest that the signaling cross-talk between saturated fatty acid palmitate and TNF-α may be a key driver in obesity-associated chronic inflammation via an excessive production of IL-8.
    Keywords:  free fatty acids; inflammation; interleukin-8; toll-like receptor 4; tumor necrosis factor-alpha
    DOI:  https://doi.org/10.3390/ijms20174112
  5. J Biomed Mater Res A. 2019 Aug 20.
    Short-term hypoxia promotes vascularization in co-culture system consisting of primary human osteoblasts and outgrowth endothelial cells.
    Bin Ma, Ming Li, Sabine Fuchs, Iris Bischoff, Alexander Hofmann, Ronald E Unger, Charles J Kirkpatrick.
      Prevascularization of tissue constructs before implantation has been developed as a novel and promising concept for successful implantation. Since hypoxia might induce angiogenesis, we have investigated the effects of hypoxic treatment on vascularization by using co-cultures of primary human osteoblasts (POBs) and outgrowth endothelial cells (OECs). Our results show that: (a) repeated short-term hypoxia (2% O2 for 8 h), not long-term hypoxia (2% O2 for 24 h), over 1 or 2 weeks, significantly enhances microvessel formation in co-cultures; (b) sustained hypoxia, not short-term or long-term hypoxia, causes cytotoxicity in mono- and co-cultures; (c) the expression of some angiogenic and inflammatory factors such as vascular endothelial growth factor (VEGF), platelet-derived growth factor subunit B (PDGF-b), insulin-like growth factor 1 (IGF-1), interleukin-8 (IL-8), and early growth response protein 1 (EGR-1) increases significantly in hypoxia-treated POB monoculture and co-cultures after single or multiple 8-h or 24-h hypoxic treatments; (d) long-term (24 h) hypoxic treatment induces more angiogenic inhibitors compared with short-term hypoxic treatment. Our findings suggest that hypoxia-induced vascularization/angiogenesis is regulated by a complex balance of angiogenic/anti-angiogenic factors, and that repeated short-term hypoxia, but not repeated long-term hypoxia, promotes the vascularization and tissue regeneration of bone tissue constructs. This article is protected by copyright. All rights reserved.
    Keywords:  Hypoxia; bone engineering; outgrowth endothelial cell; primary osteoblast; vascularization/angiogenesis
    DOI:  https://doi.org/10.1002/jbm.a.36786
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