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Mmp9 melanoma

Xin Tan, Aizhang Xu, Tuo Zhao, Qin Zhao, Jun Zhang, Cuihong Fan, Yulin Deng, Andrew Freywald, Harald Genth, Jim Xiang
Simulated microgravity (SMG) was reported to affect tumor cell proliferation and metastasis. However, the underlying mechanism is elusive. In this study, we demonstrate that clinostat-modelled SMG reduces BL6-10 melanoma cell proliferation, adhesion and invasiveness in vitro and decreases tumor lung metastasis in vivo. It down-regulates metastasis-related integrin α6β4, MMP9 and Met72 molecules. SMG significantly reduces formation of focal adhesions and activation of focal adhesion kinase (FAK) and Rho family proteins (RhoA, Rac1 and Cdc42) and of mTORC1 kinase, but activates AMPK and ULK1 kinases...
February 28, 2018: Scientific Reports
Curtis J Perry, Andrés R Muñoz-Rojas, Katrina M Meeth, Laura N Kellman, Robert A Amezquita, Durga Thakral, Victor Y Du, Jake Xiao Wang, William Damsky, Alexandra L Kuhlmann, Joel W Sher, Marcus Bosenberg, Kathryn Miller-Jensen, Susan M Kaech
Eliciting effective antitumor immune responses in patients who fail checkpoint inhibitor therapy is a critical challenge in cancer immunotherapy, and in such patients, tumor-associated myeloid cells and macrophages (TAMs) are promising therapeutic targets. We demonstrate in an autochthonous, poorly immunogenic mouse model of melanoma that combination therapy with an agonistic anti-CD40 mAb and CSF-1R inhibitor potently suppressed tumor growth. Microwell assays to measure multiplex protein secretion by single cells identified that untreated tumors have distinct TAM subpopulations secreting MMP9 or cosecreting CCL17/22, characteristic of an M2-like state...
February 7, 2018: Journal of Experimental Medicine
Yuqing Liu, Xiaofan Wei, Lizhao Guan, Sidi Xu, Yang Yuan, Danyu Lv, Xiaokun He, Jun Zhan, Yan Kong, Jun Guo, Hongquan Zhang
Unconventional myosin VIIA (Myo7a) is an actin-based motor molecule that normally functions in cochlear hair cells of the inner ear. Mutations of MYO7A/Myo7a have been implicated in inherited deafness in both humans and mice. However, there is limited information about the functions of Myo7a outside of the specialized cells of the ears. Herein, we report a previously-unidentified function of Myo7a by demonstrating that it plays an important role in melanoma progression. We found that silencing Myo7a by RNAi inhibited melanoma cell growth by upregulation of cell cycle regulator p21 and suppressed melanoma cell migration and invasion by downregulation of RhoGDI2 and MMP9...
January 19, 2018: Journal of Cell Science
Jiaqi Liu, Wenjie Luan, Yong Zhang, Jianying Gu, Yuedong Shi, Yanwen Yang, Zihao Feng, Fazhi Qi
Histone deacetylase 6 (HDAC6) plays an important role in oncogenic transformation and cancer metastasis. Our previous study has demonstrated that HDAC6 was highly expressed in melanoma cells, and contributed to the proliferation and metastasis of melanoma cells. However, the underlying mechanism of HDAC6 in melanoma metastasis and progression remains largely unclear. In this study, we reported that HDAC6 directly interacted with Tyrosine-protein phosphatase non-receptor type 1 (PTPN1) by performing co-immunoprecipitation (Co-IP) combined with liquid chromatography tandem mass spectrometry (LC-MS/MS)...
December 23, 2017: Biochemical and Biophysical Research Communications
Sirinun Pisamai, Anudep Rungsipipat, Chanin Kalpravidh, Gunnaporn Suriyaphol
Perturbation of cell adhesion can be essential for tumor cell invasion and metastasis, but the current knowledge on the gene expression of molecules that mediate cell adhesion in canine oral tumors is limited. The present study aimed to investigate changes in the gene expression of cell adhesion molecules (E-cadherin or CDH1, syndecan 1 or SDC1, NECTIN2 and NECTIN4), matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), in canine oral tumors, including benign tumors, oral melanoma (OM) and non-tonsillar oral squamous cell carcinoma (OSCC), by quantitative real-time reverse transcription PCR...
September 8, 2017: Research in Veterinary Science
Yinghui Xu, Yanru Wang, Hongliang Liu, Qiong Shi, Dakai Zhu, Christopher I Amos, Shenying Fang, Jeffrey E Lee, Terry Hyslop, Xin Li, Jiali Han, Qingyi Wei
Metzincins are key molecules in the degradation of the extracellular matrix and play an important role in cellular processes such as cell migration, adhesion, and cell fusion of malignant tumors, including cutaneous melanoma (CM). We hypothesized that genetic variants of the metzincin metallopeptidase family genes would be associated with CM-specific survival (CMSS). To test this hypothesis, we first performed Cox proportional hazards regression analysis to evaluate the associations between genetic variants of 75 metzincin metallopeptidase family genes and CMSS using the dataset from the genome-wide association study (GWAS) from The University of Texas MD Anderson Cancer Center (MDACC) which included 858 non-Hispanic white patients with CM, and then validated using the dataset from the Harvard GWAS study which had 409 non-Hispanic white patients with invasive CM...
January 2018: Molecular Carcinogenesis
Meiling Chen, Yuehua Li, Xiuning Sun, Baogang Zhang, Wei Li, Shuxiao Wang, Xuetao Zhu, Feng Li, Lihong Shi
Uveal melanoma (UM) is characterized by high metastasis and poor prognosis. A more improved understanding of the metastatic mechanism in UM cells is essential for the design of molecular therapy. Grb2‑associated binder 2 (Gab2) has been reported to serve important roles in the progression of various types of human cancer. However, the role of Gab2 in the migration and invasion of UM remains unclear. The present study sought to further assess the expression of Gab2 in UM and the role of Gab2 in the invasion of UM cells...
October 2017: Molecular Medicine Reports
Qiong Cheng, Jinfeng Wu, Yaohua Zhang, Xiao Liu, Nan Xu, Fuguo Zuo, Jinhua Xu
SOX4 has been reported to be abnormally expressed in many types of cancer, including melanoma. However, its role in cell proliferation and metastasis remains controversial. In this study, SOX4 was downregulated or overexpressed in A375, A2058 and A875 melanoma cells by siRNA or lentivirus transfection, respectively. Cell metastasis was observed by Transwell assay. In an aim to elucidate the underlying mechanisms, we determined the expression of nuclear factor-κB (NF-κB) by real-time PCR assay and western blot analysis...
June 16, 2017: International Journal of Molecular Medicine
Chao-Ming Hung, Yi-Chiang Hsu, Tzu-Yu Chen, Chi-Chang Chang, Mon-Juan Lee
Cyclophosphamide is indicated for the treatment of cancerous diseases such as breast cancer and cervical cancer. Recent studies have shown that cyclophosphamide may induce cancer metastasis, but the cause of this unexpected adverse effect is not fully understood. In this study, we investigate the effect of cyclophosphamide on cancer cell migration and its correlation to chemokine (C-X-C motif) receptor 4 (CXCR4), a biomarker for cancer metastasis. Two human cancer cell lines with significant difference in endogenous CXCR4 expression, the breast cancer cell line, MDA-MB-231, and the melanoma cell line, MDA-MB-435S, were treated with various concentrations of cyclophosphamide, followed by the assessment of CXCR4 expression and cell migration...
March 2017: Cell Biology International
Liang Peng, Zhigang Song, Demeng Chen, Ruixia Linghu, Yingzhe Wang, Xingyang Zhang, Xiaoxue Kou, Junlan Yang, Shunchang Jiao
GINS2, a subunit of GINS complex, is critical for the initiation of DNA replication and DNA replication fork progression. The expression of GINS2 is misregulated in many malignant tumors, such as leukemia, breast cancer and melanoma. However, the role of GINS in breast cancer remains poorly characterized. We investigate the possible effect and particular mechanism of GINS in breast cancer cells. We showed that expression of GINS2 is enriched in triple negative breast cancer (TNBC) cell lines. Furthermore, GINS2 knockdown decreased the growth, invasive ability and stem-like property of TNBC cells...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Hua-Wen Li, Tang-Bin Zou, Qing Jia, En-Qin Xia, Wen-Jun Cao, Wen Liu, Tai-Ping He, Qin Wang
BACKGROUND: Increasing evidence supports the anticancer effects of morin in vitro and in vivo. However, the role of morin-7-sulphate sodium (NaMoS), a water-soluble flavonoid derivative synthesized from morin remains unclear. The present study investigated the tumor suppression by NaMoS in mouse melanoma cells. MATERIALS AND METHODS: We synthesized the flavonoid derivative morin-7-sulphate sodium according to the method described for quercetin-sulphate derivative, and further isolated, purified and identified the compound...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
F Faião-Flores, D K Alves-Fernandes, P C Pennacchi, S Sandri, A L S A Vicente, C Scapulatempo-Neto, V L Vazquez, R M Reis, J Chauhan, C R Goding, K S Smalley, S S Maria-Engler
BRAF inhibitor (BRAFi) therapy for melanoma patients harboring the V600E mutation is initially highly effective, but almost all patients relapse within a few months. Understanding the molecular mechanisms underpinning BRAFi-based therapy is therefore an important issue. Here we identified a previously unsuspected mechanism of BRAFi resistance driven by elevated Hedgehog (Hh) pathway activation that is observed in a cohort of melanoma patients after vemurafenib treatment. Specifically, we demonstrate that melanoma cell lines, with acquired in vitro-induced vemurafenib resistance, show increased levels of glioma-associated oncogene homolog 1 and 2 (GLI1/GLI2) compared with naïve cells...
March 30, 2017: Oncogene
Hans E Grossniklaus, Qing Zhang, Shuo You, Conni McCarthy, Steffen Heegaard, Sarah E Coupland
We examined liver specimens from 15 patients with uveal melanoma (UM) who had died of their disseminated disease. We found 2 distinct growth patterns of UM metastasis: infiltrative (n = 12) and nodular (n = 3). In the infiltrative pattern, individual UM cells with a CD133+ cancer stem cell-like phenotype were present and formed aggregates of stage I <50-μm-diameter micrometastases in the sinusoidal spaces. These micrometastases appeared to expand, destroy adjacent hepatocytes, and form stage II 51- to 500-μm-diameter and then stage III >500μm-diameter metastases, which were encapsulated by collagenized fibrous septae...
November 2016: Human Pathology
Karyn Schmidt, Cailin E Joyce, Frank Buquicchio, Adam Brown, Justin Ritz, Robert J Distel, Charles H Yoon, Carl D Novina
Long non-coding RNAs (lncRNAs) have been implicated in numerous physiological processes and diseases, most notably cancers. However, little is known about the mechanism of many functional lncRNAs. We identified an abundantly expressed lncRNA associated with decreased melanoma patient survival. Increased expression of this lncRNA, SLNCR1, mediates melanoma invasion through a highly conserved sequence similar to that of the lncRNA SRA1. Using a sensitive technique we term RATA (RNA-associated transcription factor array), we show that the brain-specific homeobox protein 3a (Brn3a) and the androgen receptor (AR) bind within and adjacent to SLNCR1's conserved region, respectively...
May 31, 2016: Cell Reports
Luca Falzone, Rossella Salemi, Salvatore Travali, Aurora Scalisi, James A McCubrey, Saverio Candido, Massimo Libra
Tumor spreading is associated with the degradation of extracellular matrix proteins, mediated by the overexpression of matrix metalloproteinase 9 (MMP-9). Although, such overexpression was linked to epigenetic promoter methylation, the role of intragenic methylation was not clarified yet. Melanoma was used as tumor model to investigate the relationship between the DNA intragenic methylation ofMMP9 gene and MMP-9 overexpression at transcriptional and protein levels. Computational analysis revealed DNA hypermethylation within the intragenic CpG-2 region of MMP9 gene in melanoma samples with high MMP-9 transcript levels...
May 2016: Aging
Ruijing Tang, Yujun Xu, Feiya Ma, Jing Ren, Sunan Shen, Youwei Du, Yayi Hou, Tingting Wang
Our previous studies showed that extremely low frequency magnetic fields (ELF-MFs) inhibited tumor growth and change proportion of splenic regulatory T cells (Treg cells). Here, we focus on the effect of ELF-MFs on lung metastatic melanoma mouse model and the regulatory mechanism of ELF-MFs on the differentiation of Treg cells. Tumor-bearing mice were exposed to sham ELF-MFs and ELF-MFs (0.4 T, 7.5 Hz) 2 h/day for 27 days. Metastatic tumor burden of lung was significantly decreased after ELF-MF treatment...
February 2016: Bioelectromagnetics
Zhongling Luo, Xu Zhang, Weiqi Zeng, Juan Su, Keda Yang, Lixia Lu, Chuan Bian Lim, Wen Tang, Lisha Wu, Shuang Zhao, Xuekun Jia, Cong Peng, Xiang Chen
TRAF6 plays a crucial role in the regulation of the innate and adaptive immune responses. Although studies have shown that TRAF6 has oncogenic activity, the role of TRAF6 in melanoma is unclear. Here, we report that TRAF6 is overexpressed in primary as well as metastatic melanoma tumors and melanoma cell lines. Knockdown of TRAF6 with shRNA significantly suppressed malignant phenotypes including cell proliferation, anchorage-independent cell growth and metastasis in vitro and in vivo. Notably, we demonstrated that Basigin (BSG)/CD147, a critical molecule for cancer cell invasion and metastasis, is a novel interacting partner of TRAF6...
February 9, 2016: Oncotarget
Hongliang Yu, Jiao Chen, Sen Liu, Qian Lu, Jian He, Zhengyang Zhou, Yong Hu
To achieve a drug delivery system combining the programmable long circulation and targeting ability, surface engineering nanoparticles (NPs), having a sandwich structure consisting of a long circulating outmost layer, a targeting middle layer and a hydrophobic innermost core were constructed by mixing a matrix metalloproteinase MMP2 and MMP9-sensitive copolymers (mPEG-Pep-PCL) and folate receptor targeted copolymers (FA-PEG-PCL). Their physiochemical traits including morphology, particle size, drug loading content, and in vitro release profiles were studied...
October 28, 2015: Journal of Controlled Release: Official Journal of the Controlled Release Society
Qiu Tang, Jun Jiang, Jian Liu
In order to understand how tumor cells can escape immune surveillance mechanisms and thus develop antitumor therapies, it is critically important to investigate the mechanisms by which the immune system interacts with the tumor microenvironment. In our current study, we found that chemokine receptor 5 (CCR5) neutralization resulted in reduced melanoma tumor size, decreased percentage of CD11b+ Gr-1(+) myeloid-derived suppressor cells (MDSCs), and increased proportion of cluster of differentiation (CD)3+ T cells in tumor tissues...
December 2015: Inflammation
Junyun Wang, Nan Ding, Yongjun Li, Hua Cheng, Dong Wang, Qiong Yang, Youhui Deng, Yaran Yang, Yanming Li, Xiuyan Ruan, Fang Xie, Hua Zhao, Xiangdong Fang
The insulin-like growth factor binding protein 5 (IGFBP5), which is often dysregulated in human cancers, plays a crucial role in carcinogenesis and cancer development. However, the function and underlying mechanism of IGFBP5 in tumor growth and metastasis has been elusive, particularly in malignant human melanoma. Here, we reported that IGFBP5 acts as an important tumor suppressor in melanoma tumorigenicity and metastasis by a series of experiments including transwell assay, xenograft model, in vivo tumor metastasis experiment, and RNA-Seq...
August 21, 2015: Oncotarget
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