scholarly journals The role of extracellular matrix in tumour angiogenesis: the throne has NOx servants

2020 ◽  
Vol 48 (6) ◽  
pp. 2539-2555
Author(s):  
Amir M. Alsharabasy ◽  
Sharon A. Glynn ◽  
Abhay Pandit

The extracellular matrix (ECM) dynamics in tumour tissue are deregulated compared to the ECM in healthy tissue along with disorganized architecture and irregular behaviour of the residing cells. Nitric oxide (NO) as a pleiotropic molecule exerts different effects on the components of the ECM driving or inhibiting augmented angiogenesis and tumour progression and tumour cell proliferation and metastasis. These effects rely on the concentration of NO within the tumour tissue, the nature of the surrounding microenvironment and the sensitivity of resident cells to NO. In this review article, we summarize the recent findings on the correlation between the levels of NO and the ECM components towards the modulation of tumour angiogenesis in different types of cancers. These are discussed principally in the context of how NO modulates the expression of ECM proteins resulting in either the promotion or inhibition of tumour growth via tumour angiogenesis. Furthermore, the regulatory effects of individual ECM components on the expression of the NO synthase enzymes and NO production were reviewed. These findings support the current efforts for developing effective therapeutics for cancers.

Author(s):  
Dan Liu ◽  
Marwa Mahmoud ◽  
Carla Milagre ◽  
Ian Zachary ◽  
Paul Frankel

Endocrinology ◽  
2020 ◽  
Author(s):  
Peiyi Xie ◽  
Hui Wang ◽  
Jiayu Fang ◽  
Dongnian Du ◽  
Ze Tian ◽  
...  

Abstract COP9 signalosome subunit 5 (CSN5) plays a key role in carcinogenesis of multiple cancers, and contributes to stabilization of target proteins through deubiquitylation. However, the underlying role of CSN5 in thyroid carcinoma has not been reported. In this research, our data showed that CSN5 was overexpressed in thyroid carcinoma tissues compared with para-cancerous tissues. Furthermore, a series of gain/loss functional assays were performed to demonstrate the role of CSN5 in facilitating thyroid carcinoma cell proliferation and metastasis. Additionally, we found that there was a positive correlation between CSN5 and angiopoietin-like protein 2 (ANGPTL2) protein levels in thyroid carcinoma tissues and that CSN5 promoted thyroid carcinoma cell proliferation and metastasis through ANGPTL2. We also identified the underlying mechanism that CSN5 elevated ANGPTL2 protein level through directly binding it, and decreasing its ubiquitination and degradation. Overall, our results highlight the significance of CSN5 in promoting thyroid carcinoma carcinogenesis and implicate CSN5 as a promising candidate for thyroid carcinoma treatment.


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Bin Wang ◽  
Zheng-sheng Wu ◽  
Qiang Wu

Glioma is one of the most common primary malignant brain tumors and the outcomes are generally poor. The intrinsic mechanisms involved in glioma development and progression remain unclear. Further studies are urgent and necessary. In this study, we have proven that CMIP (C-Maf-inducing protein) promotes cell proliferation and metastasis in A172 cells through knockdown of CMIP and in U251 cells through overexpression of CMIP by using MTT assay, cell colony formation assay, cell migration assay, and cell invasion assay. Furthermore, we discovered that CMIP upregulates MDM2, which is involved in the promoting role of CMIP in human glioma cells. For clinical study, 99 glioma tissues and 59 normal tissues were analyzed. CMIP expression was higher in glioma tissues than in normal tissues. In glioma tissues, CMIP is found to correlate positively with tumor grade but no significant correlation is found with patients’ age, gender, or Karnofsky performance score (KPS). Moreover, CMIP also correlates with low relapse-free survival (RFS) rate and overall survival (OS) rate in glioma patients. Therefore, CMIP is oncogenic and could be a potential target for human glioma diagnosis and therapy.


2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Shan Gao ◽  
Jingcheng Jiang ◽  
Pan Li ◽  
Huijuan Song ◽  
Weiwei Wang ◽  
...  

Metformin is one of the most widely prescribed antidiabetics for type 2 diabetes. A critical role of metformin against tumorigenesis has recently been implicated, although several studies also reported the lack of anticancer property of the antidiabetics. Given the controversies regarding the potential role of metformin against tumour progression, the effect of metformin against breast, cervical, and ovarian tumour cell lines was examined followed byin vivoassessment of metformin on tumour growth using xenograft breast cancer models. Significant inhibitory impact of metformin was observed in MCF-7, HeLa, and SKOV-3 cells, suggesting an antiproliferative property of metformin against breast, cervical, and ovarian tumour cells, respectively, with the breast tumour cells, MCF-7, being the most responsive.In vivoassessment was subsequently carried out, where mice with breast tumours were treated with metformin (20 mg/kg body weight) or sterile PBS solution for 15 consecutive days. No inhibition of breast tumour progression was detected. However, tumour necrosis was significantly increased in the metformin-treated group, accompanied by decreased capillary formation within the tumours. Thus, despite the lack of short-term benefit of metformin against tumour progression, a preventive role of metformin against breast cancer was implicated, which is at partially attributable to the attenuation of tumour angiogenesis.


Pancreatology ◽  
2018 ◽  
Vol 18 (4) ◽  
pp. S152
Author(s):  
Andrea Rech ◽  
Qikun Wang ◽  
Felix Rueckert ◽  
Prama Pallavi

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Luyang Zhang ◽  
Yunjian Wang ◽  
Ling Zhang ◽  
Guohua You ◽  
Congyu Li ◽  
...  

Abstract Background Pancreatic cancer (PC) is one of the deadliest cancers about the digestive system. Recent researches have validated that long non-coding RNAs (lncRNAs) play vital roles in various cancers, while the function of LINC01006 in PC is rarely clarified. Aim of the study Investigation of the specific role of LINC01006 in PC. Methods LINC01006 expression was examined by RT-qPCR. CCK-8, EdU, transwell, wound healing, and western blot assays were carried out to explore the function of LINC01006 in PC. The interaction among LINC01006, miR-2682-5p and HOXB8 was verified by luciferase reporter, RIP and ChIP assays. Results The expression of LINC01006 was markedly upregulated in PC tissues and cells. Furthermore, LINC01006 knockdown inhibited PC cell proliferation, invasion and migration, and upregulation of LINC01006 led to the opposite results. Besides, miR-2682-5p expression was downregulated and negatively regulated by LINC01006 in PC. Meanwhile, LINC01006 could bind with miR-2682-5p in PC. Moreover, miR-2682-5p negatively regulated HOXB8 expression and there was a binding site between miR-2682-5p and HOXB8 in PC. Additionally, miR-2682-5p overexpression or HOXB8 knockdown rescued the promotive effects of LINC01006 upregulation on PC cell progression. Similarly, miR-2682-5p inhibition or HOXB8 overexpression countervailed the repressive role of LINC01006 downregulation in PC cell progression. In addition, the transcription factor HOXB8 could activate LINC01006 transcription in PC. Conclusions LINC01006 promotes cell proliferation and metastasis in pancreatic cancer via miR-2682-5p/HOXB8 axis, which may facilitate the treatment for PC.


Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3259 ◽  
Author(s):  
Jingyi Song ◽  
Qingxia Ma ◽  
Ming Hu ◽  
Dongmeng Qian ◽  
Bin Wang ◽  
...  

Glioblastoma (GBM), the most common type of primary tumor in the central nervous system, is a very aggressive brain tumor with poor prognosis and a high recurrence rate. Increasing evidence suggests that human cytomegalovirus (HCMV) infection is related to GBM and leads to GBM cell growth and metastasis. MicroRNAs are important regulators in the growth and metastasis of glioblastoma. This study aimed to demonstrate the role of miR-144-3p in HCMV-positive glioblastoma. We found that, after HCMV infection, the expression of miR-144-3p decreased, whereas the expression of TOP2A increased. Bioinformatics analyses indicated that miR-144-3p directly targets the TOP2A 3′-UTR (Untranslated Region). We discovered that the overexpression of miR-144-3p downregulated the overexpression of TOP2A and inhibited the proliferation, clone formation, and invasion of HCMV-positive glioma in vitro. Taken together, these results show that miR-144-3p inhibited growth and promoted apoptosis in glioma cells by targeting TOP2A.


1991 ◽  
Vol 331 (1261) ◽  
pp. 323-335 ◽  

As neurons grow to their targets their processes elongate, branch and form specialized endings into which are inserted appropriate ion channels. Our aim has been to analyse the role of the extracellular matrix molecules laminin and tenascin in inducing growth and in determining the form and physiological properties of growing neurites. A preparation in which development and regeneration can be followed at the cellular and molecular level in the animal and in tissue culture is the central nervous system (CNS) of the leech. In leech extracellular matrix (ECM) both laminin and tenascin are present; the molecules are structurally similar but not identical to their vertebrate counterparts. Tenascin extracted from leech ECM shows a typical hexabrachial structure whereas laminin shows a typical cruciform structure in rotary shadowed preparations. Leech laminin purified by means of a monoclonal antibody is a molecule of about 1000 kDa, with a polypeptide composition of 340, 200, 180 and 160 kDa. Substrates that contain tenascin or laminin produce rapid and reliable outgrowth of neurites by identified cells. A remarkable finding is that the outgrowth pattern produced by an individual neuron depends in part on its identity, in part on the substrate upon which it is placed. For example, a Retzius cell grows in a quite different configuration and far more rapidly on laminin substrate than does another type of neuron containing the same transmitter (serotonin); and the pattern of outgrowth of the Retzius cell is different on laminin and on the plant lectin Con A (concanavalin A). Thus Con A induces the growth of processes that are shorter, thicker, more curved and contain fewer calcium channels than those grown on laminin. To determine whether laminin can also influence neurite outgrowth in the animal, immunocytological techniques have been used to follow its distribution in the extracellular matrix of normal, developing and regenerating leech CNS. In adult leeches neuronal processes in the CNS are not in contact with laminin which is confined to the surrounding extracellular matrix. In embryos however, laminin staining appears between ganglionic primordia along the pathways that neurons will follow. Similarly, after injury to the adult CNS, laminin accumulates at the very sites at which sprouting and regeneration begin. How the laminin becomes redistributed to appear in the region of injury has not yet been established. Together these findings suggest a key role for laminin and for other extracellular matrix molecules. One attractive speculation is that large molecules situated at a particular region of the CNS may give differential instructions to different types of neurons, causing branching in some, accelerated outgrowth in others and formation of specialized endings in still others. This represents an economical scheme by which relatively few molecules could exert diverse effects.


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