HIF-α/MIF and NF-κB/IL-6 Axes Contribute to the Recruitment of CD11b+Gr-1+ Myeloid Cells in Hypoxic Microenvironment of HNSCC

Zhu, Guiquan; Tang, Yaling; Geng, Ning; Zheng, Min; Jiang, Jian; Li, Ling; Li, Kaide; Lei, Zhengge; Chen, Wei; Fan, Yunlong; Ma, Xiangrui; Li, Longjiang; Wang, Xiaoyi; Liang, Xin‐hua

doi:10.1593/neo.132034

Cited by 62 publications

(52 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The Lenti-X shRNA expression system (Clontech) was used for the shRNA-mediated inhibition of HIF-1a and HIF-2a expression, and the knocking down efficiency of HIF-1a and HIF-2a lentiviral shRNAs has been demonstrated in our previous study (29). To knock down miR-21 expression, oligonucleotides against miR-21 were annealed and cloned into the lentiviral vector pLenti-U6-pgkpuro as described previously (30).…”

Section: Shrna Cloning and Lentiviral Packagingmentioning

confidence: 99%

Exosomes Derived from Hypoxic Oral Squamous Cell Carcinoma Cells Deliver miR-21 to Normoxic Cells to Elicit a Prometastatic Phenotype

et al. 2016

Self Cite

View full text Add to dashboard Cite

Hypoxia is a common feature of solid tumors and is associated with aggressiveness and poor patient outcomes. Exosomes, initially considered to be cellular "garbage dumpsters," are now implicated in mediating interactions with the cellular environment. However, the mechanisms underlying the association between exosomes and hypoxia during cancer progression remain poorly understood. In this study, we found that exosomes derived from hypoxic oral squamous cell carcinoma (OSCC) cells increased the migration and invasion of OSCC cells in a HIF1a and HIF-2a-dependent manner. Given that exosomes have been shown to transport miRNAs to alter cellular functions, we performed miRNA sequencing of normoxic and hypoxic OSCCderived exosomes. Of the 108 miRNAs that were differentially expressed, miR-21 stood out as one of the most significantly upregulated miRNAs under hypoxic conditions. miR-21 depletion in hypoxic OSCC cells led to decreased miR-21 levels in exosomes and significantly reduced cell migration and invasion. Conversely, restoration of miR-21 expression in HIF-1a and HIF2a-depleted exosomes rescued OSCC cell migration and invasion. Moreover, exosomal miR-21 markedly enhanced snail and vimentin expression, while significantly decreasing E-cadherin levels in OSCC cells, in vitro and in vivo. Finally, circulating exosomal miR-21 levels were closely associated with HIF-1a/ HIF-2a expression, T stage, and lymph node metastasis in patients with OSCC. In conclusion, our findings suggest that the hypoxic microenvironment may stimulate tumor cells to generate miR-21-rich exosomes that are delivered to normoxic cells to promote prometastatic behaviors and prompt further investigation into the therapeutic value of exosome inhibition for cancer treatment.

show abstract

Section: Shrna Cloning and Lentiviral Packagingmentioning

confidence: 99%

Exosomes Derived from Hypoxic Oral Squamous Cell Carcinoma Cells Deliver miR-21 to Normoxic Cells to Elicit a Prometastatic Phenotype

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…and that diverse types of cancer can secrete signaling molecules that disrupt the immune responses [51,68]; interaction between cancer and stroma may allow a tumor escape rejection, even after being recognized by adaptive immunity [100]. Carcinoma cells through secretion of IL-6, IL-8, CXCL10, and CCL5, (their expression depending on RelA) overcome the control of Hypoxia-Induced Factors (HIF) and induce CD11b+Gr-1+ myeloid cells to promote tumor growth and angiogenesis [101]. Loss of the control of cytokine expression by the NF-κB /p53 interaction network, enables immunosuppression and disruption of tissue integrity, in spite of signals for regeneration.…”

Section: Nf-κb Effects On Tissue: Shaping the Microenvironmentmentioning

confidence: 99%

Dynamic aberrant NF-κB spurs tumorigenesis: A new model encompassing the microenvironment

Vlahopoulos¹,

Çen²,

Hengen³

et al. 2015

Cytokine & Growth Factor Reviews

View full text Add to dashboard Cite

Recently it was discovered that a transient activation of transcription factor NF-κB can give cells properties essential for invasiveness and cancer initiating potential. In contrast, most oncogenes to date were characterized on the basis of mutations or by their constitutive overexpression. Study of NF-κB actually leads to a far more dynamic perspective on cancer: tumors caused by diverse oncogenes apparently evolve into cancer after loss of feedback regulation for NF-κB. This event alters the cellular phenotype and the expression of hormonal mediators, modifying signals between diverse cell types in a tissue. The result is a disruption of stem cell hierarchy in the tissue, and pervasive changes in the microenvironment and immune response to the malignant cells.

show abstract

“…HIF-1α was identified as an effector in increase of cell number, inhibition of proliferation in various cell types given inadequate supply of oxygen [21][22][23][24]. Since we observed the hypoxia-induced inhibition of apoptosis and enhancement of proliferation was attenuated by resveratrol, we suspected this reversal may be related to HIF-1α, an established marker of cellular response to hypoxia.…”

Section: Suppression Of Hif-1α Accounts For Attenuation On Proliferatmentioning

confidence: 84%

Resveratrol Inhibits Proliferation and Promotes Apoptosis of Keloid Fibroblasts by Targeting HIF-1α

Si¹,

Qin²,

Xiao³

et al. 2017

J Clin Exp Dermatol Res

View full text Add to dashboard Cite

Keloid is characterized by red, tickling, hard and irregular raised tissues, and tends to outgrow its origin. It occurs frequently in young adults and appears as refractory to prevailing therapies. Although histological studies have revealed striking similarities of keloids with cancer, such as uncontrolled cell growth, and many of the therapies in clinical practice including -fluorouracil and tamoxifen, excision, and radiation therapy were borrowed from cancer management, the etiology of keloid has remained to be explored to provide insights for developing effective therapeutic modalities. Hypoxic stress around tumors was frequently reported as conferring growth momentum to tumor cells. The hypoxia caused by fast growing of keloid fibroblasts may also be a risk factor that antagonizes therapies. Resveratrol has received intense attention in cancer researches since its anti-proliferative effect on human pulmonary artery smooth muscle cells were revealed. In this study, we first revealed that hypoxia promotes proliferation and inhibit apoptosis of keloid fibroblasts, which highlights the potential obstacle in treating keloids. Further, we demonstrated resveratrol could reverse the effect of hypoxia on keloids, which involves down-regulation of HIF-1α. Moreover, the collagen synthesis of keloid fibroblasts was also inhibited by resveratrol, which was corresponding with HIF-1α suppression. These results provide complementary evidence to the multiple molecular signalings controlled by resveratrol and suggest a pathway implicates resveratrol to regulate expression of procollagen expression via HIF-1α.

show abstract

HIF-α/MIF and NF-κB/IL-6 Axes Contribute to the Recruitment of CD11b+Gr-1+ Myeloid Cells in Hypoxic Microenvironment of HNSCC

Cited by 62 publications

References 51 publications

Exosomes Derived from Hypoxic Oral Squamous Cell Carcinoma Cells Deliver miR-21 to Normoxic Cells to Elicit a Prometastatic Phenotype

Exosomes Derived from Hypoxic Oral Squamous Cell Carcinoma Cells Deliver miR-21 to Normoxic Cells to Elicit a Prometastatic Phenotype

Dynamic aberrant NF-κB spurs tumorigenesis: A new model encompassing the microenvironment

Resveratrol Inhibits Proliferation and Promotes Apoptosis of Keloid Fibroblasts by Targeting HIF-1α

Contact Info

Product

Resources

About