The interaction of HspA1A with TLR2 and TLR4 in the response of neutrophils induced by ovarian cancer cells in vitro

Klink, Magdalena; Nowak, Marek; Kiełbik, Michał; Bednarska, Katarzyna; Blus, Edyta; Szpakowski, M; Szyłło, Krzysztof; Sułowska, Zofia

doi:10.1007/s12192-012-0338-2

Cited by 25 publications

(19 citation statements)

References 50 publications

(73 reference statements)

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“…4a ). Furthermore, many genes known to regulate survival of different epithelial cell types are present in that list, including Sgk1 , Id1 , Vdr , Bcl2l14 , Dusp1 , Bmx and Igfbp3 (mammary gland), Pgf , Irf5 , Pla2g4a and Pmepa1 (intestine), and Hspa1a (ovary) 34 35 36 . Finally, several members of key pathways regulating cell survival/death were among sexually dimorphic genes: heat shock proteins ( Hspa1a , Hspa1b , Hspa2 , Hspb1 ) and members of the p53 ( Rnd3 , Plk2 , Sgpl1 , Igfbp3 , Pmepa1 ), Pi3k/Akt ( Pik3r1 , Pdgfc , Fn1 ) and Fas/caspases pathways ( Mcl1 , Hspa1b , Fn1 , Bcl2l14 , Lum ).…”

Section: Resultsmentioning

confidence: 99%

Sex hormones have pervasive effects on thymic epithelial cells

Dumont-Lagacé

St-Pierre

Perreault

2015

Sci Rep

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The goal of our study was to evaluate at the systems-level, the effect of sex hormones on thymic epithelial cells (TECs). To this end, we sequenced the transcriptome of cortical and medullary TECs (cTECs and mTECs) from three groups of 6 month-old mice: males, females and males castrated at four weeks of age. In parallel, we analyzed variations in the size of TEC subsets in those three groups between 1 and 12 months of age. We report that sex hormones have pervasive effects on the transcriptome of TECs. These effects were exquisitely TEC-subset specific. Sexual dimorphism was particularly conspicuous in cTECs. Male cTECs displayed low proliferation rates that correlated with low expression of Foxn1 and its main targets. Furthermore, male cTECs expressed relatively low levels of genes instrumental in thymocyte expansion (e.g., Dll4) and positive selection (Psmb11 and Ctsl). Nevertheless, cTECs were more abundant in males than females. Accumulation of cTECs in males correlated with differential expression of genes regulating cell survival in cTECs and cell differentiation in mTECs. The sexual dimorphism of TECs highlighted here may be mechanistically linked to the well-recognized sex differences in susceptibility to infections and autoimmune diseases.The immune system of vertebrates shows a major sexual dimorphism. Thus, relative to males, females usually display stronger immune response to vaccination and infection but suffer a higher propensity to many autoimmune diseases 1-4 . Though we have limited insight into the mechanistic bases for these differences 4 , evidence suggests that they result from both direct and indirect effects of sex steroids on innate and adaptive immune responses. Thus, sex hormones can affect immune cells directly or via modulation of the gut microbiome which in turn influences the immune response 5-9 . Sex-based differences in thymus biology have been observed in many studies. Thymic involution, which affects all vertebrates 10,11 , accelerates at puberty and progresses at different rates in males and females [12][13][14] . Also, administration and ablation of androgens respectively accelerates and reverses, albeit transiently, thymic involution [15][16][17][18][19] . Nevertheless, it remains unclear to what degree sex steroids' impact on thymic cellularity may reflect the influence of hormones on thymic epithelial cells (TECs) 3 vs. other cell types (thymocytes, mesenchymal cells).Recent studies have shown that sex steroids do affect TECs. In adult mice, cortical and medullary TECs (cTECs and mTECs) have slower proliferation rates in males than females 20 . Furthermore, following acute ablation in a transgenic mouse model, cTECs were found to regenerate in females and castrated (Cx) males, but not in males or androgen-treated females 21 . Finally, it was recently shown that, in TECs, androgens repress transcription of the Notch ligand Dll4 22 which is essential for specification, commitment, and development of thymocytes 23 . Nevertheless, studies in other cell types (e.g., liver, adip...

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Section: Resultsmentioning

confidence: 99%

Sex hormones have pervasive effects on thymic epithelial cells

Dumont-Lagacé

St-Pierre

Perreault

2015

Sci Rep

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“…Hsp70 could increase tumor cell invasiveness through its ability to trigger an inflammatory tumor microenvironment. Besides activating antigen-presenting cells (APCs), free extracellular Hsp70 released from ovarian cancer cells has been shown to activate neutrophils and subsequent reactive oxygen species (ROS) production via TLR2/4 signaling [ 173 ]. ROS promote angiogenesis and metastasis via stimulation of vascular endothelial growth factor production [ 174 ] and activation of MMPs [ 175 ].…”

Section: Extracellular Functions Of Hsp70mentioning

confidence: 99%

The Complex Function of Hsp70 in Metastatic Cancer

Juhász¹,

Lipp²,

Nimmervoll³

et al. 2013

Cancers

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Elevated expression of the inducible heat shock protein 70 (Hsp70) is known to correlate with poor prognosis in many cancers. Hsp70 confers survival advantage as well as resistance to chemotherapeutic agents, and promotes tumor cell invasion. At the same time, tumor-derived extracellular Hsp70 has been recognized as a “chaperokine”, activating antitumor immunity. In this review we discuss localization dependent functions of Hsp70 in the context of invasive cancer. Understanding the molecular principles of metastasis formation steps, as well as interactions of the tumor cells with the microenvironment and the immune system is essential for fighting metastatic cancer. Although Hsp70 has been implicated in different steps of the metastatic process, the exact mechanisms of its action remain to be explored. Known and potential functions of Hsp70 in controlling or modulating of invasion and metastasis are discussed.

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“…TLR4 can mediate MyD88-dependent pathways through the interaction with a series of cytokines to promote tumorigenesis ( 31 ). Clinical studies also found that TLR4 was correlated with the growth and metastasis of gastric cancer ( 32 ), ovarian cancer ( 33 , 34 ), cervical cancer ( 35 ), and other types of tumor cells. In our study, we found that TLR4 was positively expressed in 58.33% cases of breast cancer tissues and in 90.57% cases of adjacent non-cancerous tissue.…”

Section: Discussionmentioning

confidence: 99%

Expression and clinical significance of SATB1 and TLR4 in breast cancer

Wang

et al. 2017

Oncology Letters

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This study investigated the expression of special AT-rich sequence-binding protein 1 (SATB1) and toll-like receptor 4 (TLR4) protein in breast cancer and its clinical significance. We collected breast cancer tissues from 120 patients and adjacent non-cancerous tissue from 53 patients. SATB1 was expressed in 89 cases of breast cancer (74.17%) and in 7 cases of adjacent non-cancerous tissue (13.21%). TLR4 was expressed in 70 cases of breast cancer tissues (58.33%) and in 48 cases of adjacent non-cancerous tissue (90.57%). The differences of SATB and TLR4 in breast cancer and adjacent non-cancerous tissue were statistically significant. We found a negative correlation between the expression of SATB1 and TLR4 (r=−0.624, P<0.05). The expression of SATB1 and TLR4 were not significantly correlated with age, menopause, and PR and HER-2 protein expression, but were significantly correlated with tumor size, local lymphatic metastasis, histopathological grade, tumor stage, and ER protein expression (P<0.05). Overall, SATB1 and TLR4 proteins are involved in the development of breast cancer, a finding of great significance to identify therapeutic targets and prognosis markers for breast cancer.

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The interaction of HspA1A with TLR2 and TLR4 in the response of neutrophils induced by ovarian cancer cells in vitro

Cited by 25 publications

References 50 publications

Sex hormones have pervasive effects on thymic epithelial cells

Sex hormones have pervasive effects on thymic epithelial cells

The Complex Function of Hsp70 in Metastatic Cancer

Expression and clinical significance of SATB1 and TLR4 in breast cancer

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