Obesity and cancer phenotype: Is angiogenesis a missed link?

Mendonça, Fernando; Soares, Raquel

doi:10.1016/j.lfs.2015.08.009

Cited by 15 publications

(13 citation statements)

References 102 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Adipose tissue is defined as a lipid store depot, inflammatory and endocrine organ (Mendonça and Soares 2015). Thus, it provides a chronic low-grade inflammatory condition potentiated by the presence of multiple cytokines and hormones, sometimes associated with disease.…”

Section: Discussionmentioning

confidence: 99%

Adipocyte proteome and secretome influence inflammatory and hormone pathways in glioma

et al. 2018

View full text Add to dashboard Cite

Gliomas represent the most common primary malignant brain tumors in adults, with an extremely poor prognosis. Among several risk factors, lifestyle was also recently identified as a major risk factor for the development of primary glioma. In the present study, we explore the relationship between obesity and glioma in a cellular model. Thus, we have study the influence of adipocytes secretome on glioma cell line GL261. Using the 3T3-L1 adipocyte cell line, and its conditioned medium (adipokines-enriched medium), we showed that adipocyte-released factors relate with glioma angiogenic, growth, hormones and metabolic behavior by MALDI-TOF-MS and proteomic array analysis. In a first view, STI1, hnRNPs and PGK1 are under expressed on CGl. Similarly, both carbonic anhydrase and aldose reductase are even suppressed in glioma cells that grown under adipokines-enriched environment. Contrariwise, RFC1, KIF5C, ANXA2, N-RAP and RACK1 are overexpressed in GL261 cell the in the presence of the adipokines-enriched medium. We further identified the factors that are released by adipocyte cells, and revealed that several pro-inflammatory and angiogenic factors, such as IL-6, IL-11, LIF, PAI-1, TNF-α, endocan, HGF, VEGF IGF-I, were secreted to the medium into a high extent, whereas TIMP-1 and SerpinE1 were under expressed on CGl. This study discloses an interesting in vitro model for the study of glioma biology under a Bobesity^ environment, that can be explored for the understanding of cancer cells biology, for the search of biomarkers, prognostic markers and therapeutic approaches.

show abstract

Section: Discussionmentioning

confidence: 99%

Adipocyte proteome and secretome influence inflammatory and hormone pathways in glioma

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Adipose tissue is no longer considered a mere lipid store depot, but also an inflammatory and endocrine organ [Monteiro, ; Mendonça and Soares, ]. Accordingly, obesity provides a chronic low grade inflammatory condition, further potentiated by the presence of hormone cues and cytokines, which are strongly associated with disease.…”

Section: Discussionmentioning

confidence: 99%

Effect of Adipocyte Secretome in Melanoma Progression and Vasculogenic Mimicry

Coelho

Almeida

Prudêncio

et al. 2016

J of Cellular Biochemistry

Self Cite

View full text Add to dashboard Cite

Obesity, favored by the modern lifestyle, acquired epidemic proportions nowadays. Obesity has been associated with various major causes of death and morbidity including malignant neoplasms. This increased prevalence has been accompanied by a worldwide increase in cutaneous melanoma incidence rates during the last decades. Obesity involvement in melanoma aetiology has been recognized, but the implicated mechanisms remain unclear. In the present study, we address this relationship and investigate the influence of adipocytes secretome on B16-F10 and MeWo melanoma cell lines. Using the 3T3-L1 adipocyte cell line, as well as ex vivo subcutaneous (SAT) and visceral (VAT) adipose tissue conditioned medium, we were able to show that adipocyte-released factors play a dual role in increasing melanoma cell overall survival, both by enhancing proliferation and decreasing apoptosis. B16-F10 cell migration and cell-cell and cell-matrix adhesion capacity were predominantly enhanced in the presence of SAT and VAT released factors. Melanocytes morphology and melanin content were also altered by exposure to adipocyte conditioned medium disclosing a more dedifferentiated phenotype of melanocytes. In addition, exposure to adipocyte-secreted molecules induced melanocytes to rearrange, on 3D cultures, into vessel-like structures, and generate characteristic vasculogenic mimicry patterns. These findings are corroborated by the released factors profile of 3T3-L1, SAT, and VAT assessed by microarrays, and led us to highlight the mechanisms by which adipose secretome from sub-cutaneous or visceral depots promote melanoma progression. J. Cell. Biochem. 117: 1697-1706, 2016. © 2015 Wiley Periodicals, Inc.

show abstract

“…Hence, a thorough understanding of the long sought-after relationship between metabolic diseases and cancers will not only provide early biomarkers for disease progression, but will also elucidate novel therapeutic targets to decrease cancer-associated complications. Furthermore, since tremendous increases in metabolic syndrome are being reported in younger adults [4], which makes them more susceptible to malignancies later in life, studies on the common etiologies in metabolic diseases and cancer are garnering a lot of attention [7,17,[18][19][20][21][22].…”

mentioning

confidence: 99%

Tripping on TRIB3 at the junction of health, metabolic dysfunction and cancer

2016

View full text Add to dashboard Cite

Metabolic diseases like obesity, atherosclerosis and diabetes are frequently associated with increased risk of aggressive cancers. Although metabolic dysfunctions in normal cells are manifested due to defective signaling networks that control cellular homeostasis, malignant cells utilize these signaling networks for their increased survival, growth and metastasis. Despite decades of research, a common mechanistic link between these chronic pathologies is still not well delineated. Evidences show that the unfolded protein response (UPR) and the endoplasmic reticulum stress (ERS) pathways are often dysregulated in both metabolic diseases and cancer. The UPR also triggers coordinated signaling with both PI3K/AKT/mTOR and Autophagy pathways in order to promote stress-adaptive mechanisms. Whereas, uncontrolled UPR and the resultant ERS escalates cells towards metabolic dysfunctions and ultimately cell death. In this review, we will discuss findings that implicate a crucial role for the multifunctional ERS-induced protein, TRIB3. The 'pseudokinase' function of TRIB3 facilitates the inactivation of multiple transcription factors and signaling proteins. The MEK1 binding domain of TRIB3 enables it to deactivate multiple MAP-kinases. In addition, the COP1 motif of TRIB3 assists ubiquitination and proteasomal degradation of numerous TRIB3 associated proteins. The most well studied action of TRIB3 has been on the PI3K/AKT/mTOR pathway, where TRIB3-mediated inhibition of AKT phosphorylation decreases insulin signaling and cell survival. Conversely, cancer cells can either upregulate the AKT survival pathway by suppressing TRIB3 expression or alter TRIB3 localization to degrade differentiation inducing nuclear transcription factors such as C/EBPα and PPARγ. The gain-of-function Q84R polymorphism in TRIB3 is associated with increased risk of diabetes and atherosclerosis. TRIB3 acts as a crucial 'stress adjusting switch' that links homeostasis, metabolic disease and cancer; and is being actively investigated as a disease biomarker and therapeutic target.

show abstract

Obesity and cancer phenotype: Is angiogenesis a missed link?

Cited by 15 publications

References 102 publications

Adipocyte proteome and secretome influence inflammatory and hormone pathways in glioma

Adipocyte proteome and secretome influence inflammatory and hormone pathways in glioma

Effect of Adipocyte Secretome in Melanoma Progression and Vasculogenic Mimicry

Tripping on TRIB3 at the junction of health, metabolic dysfunction and cancer

Contact Info

Product

Resources

About