Hyaluronan in the Tumor Microenvironment

Spinelli, Fiorella Mercedes; Vitale, Daiana Luján; Sevic, Ina; Alaniz, Laura

doi:10.1007/978-3-030-40146-7_3

Cited by 38 publications

(39 citation statements)

References 152 publications

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“…We show that OA stimulates the expression of HMMR through transcription factor CEBPα, providing another mechanism underlying HMMR expression. Hyaluronan (HA), a member of the glycosaminoglycan family, is an extracellular matrix component and interacts with various cellular receptors to promote cell growth and movement [60]. HMMR is one of defined hyaluronan cellular receptors.…”

Section: Discussionmentioning

confidence: 99%

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Oleate acid-stimulated HMMR expression by CEBPα is associated with nonalcoholic steatohepatitis and hepatocellular carcinoma

Zhang¹,

Liu²,

Xie³

et al. 2020

Int. J. Biol. Sci.

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Non-alcoholic steatohepatitis (NASH) is a type of nonalcoholic fatty liver disease and has become a major risk factor for hepatocellular carcinoma (HCC). However, the underlying pathophysiological mechanisms are still elusive. Here, we identify hyaluronan-mediated motility receptor (HMMR) as a critical gene associated with NASH/HCC by combination of bioinformatic analysis and functional experiments. Analysis of differentially expressed genes (DEGs) between normal controls and NASH/HCC identified 5 hub genes (HMMR, UBE2T, TYMS, PTTG1 and GINS2). Based on the common DEGs, analyses of univariate and multivariate Cox regression and the area under the curve (AUC) value of the receiver operating characteristic (ROC) indicate that HMMR is the most significant gene associated with NASH/HCC among five hub genes. Oleate acid (OA), one of fatty acids that induce cellular adipogenesis, stimulates HMMR expression via CCAAT/enhancer-binding protein α (CEBPα). CEBPα increases the expression of HMMR through binding to its promoter. HMMR promotes HCC cell proliferation in vitro via activation of G1/S and G2/M checkpoint transitions, concomitant with a marked increase of the positive cell cycle regulators, including cyclin D1, cyclin E, and cyclin B1. Knockdown of HMMR suppresses HCC tumor growth in nude mice. Our study identifies an important role of HMMR in NASH/HCC, and suggests that HMMR may be a useful target for therapy and prognostic prediction of NASH/HCC patients.

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Section: Discussionmentioning

confidence: 99%

“…Hyaluronan (HA), a member of the glycosaminoglycan family, is an extracellular matrix component and interacts with various cellular receptors to promote cell growth and movement 60 . HMMR is one of defined hyaluronan cellular receptors.…”

Section: Discussionmentioning

confidence: 99%

Oleate acid-stimulated HMMR expression by CEBPα is associated with nonalcoholic steatohepatitis and hepatocellular carcinoma

Zhang¹,

Liu²,

Xie³

et al. 2020

Int. J. Biol. Sci.

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“…Importantly, HAS3 enzyme produces HA of low (LMW) or middle (MMW) and is associated with metastasic behavior in some tumor cell lines [ 40 , 41 ]. Besides, it has been reported that this enzyme is the most active and predominant in pathological conditions [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that the production of HA by stromal cells is stimulated by interactions with tumor cells, but that the synthesis also increases in the malignant tumor cells themselves. Hyaluronan synthesis and degradation are strictly regulated in physiological conditions, but in the tumoral tissues they are dysregulated, originating HA of different molecular sizes, which in turn have different functions [ 42 ]. Even more, HA interaction with specific binding proteins and receptors modulating its function in tumoral context [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Hyaluronan Metabolism is Associated with DNA Repair Genes in Breast and Colorectal Cancer. Screening of Potential Progression Markers Using qPCR

et al. 2020

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In this work, we compared mRNA levels of Hyaluronan (HA) metabolism members and BRCA genes, known to be involved in the tumoral process, between tumor and non-tumor adjacent tissue and its correlation with previously proposed biomarkers (ER, PR, HER2 and KI67) in order to assess their value as a progression biomarkers. We show alteration in HA metabolism in colorectal but not breast cancer. However, we found a decrease in Hyaluronidase 1 HYAL1 levels in the breast but not colorectal cancer. We also show lower HA levels in tumor compared with normal tissue that could indicate a possible influence of tumor on its surrounding “normal” tissue. In both breast and colorectal cancer, CD44 and BRCA2 showed a strong positive correlation. Besides, our results show first indicators that qPCR of the analyzed genes could be used as an easy and low cost procedure for the evaluation of molecular markers we propose here.

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“…At the same time, they also sense changes in the biophysical properties of the TME and adapt their behavior (see below). The increased interstitial pressure of the TME impedes the access of anti-cancer drugs to the tumor mass [1,2,53].…”

Section: Fibrillar and Non-fibrillar Ecm Components Orchestrate The Bmentioning

confidence: 99%

Hold on or Cut? Integrin- and MMP-Mediated Cell–Matrix Interactions in the Tumor Microenvironment

Niland

Eble

2020

IJMS

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The tumor microenvironment (TME) has become the focus of interest in cancer research and treatment. It includes the extracellular matrix (ECM) and ECM-modifying enzymes that are secreted by cancer and neighboring cells. The ECM serves both to anchor the tumor cells embedded in it and as a means of communication between the various cellular and non-cellular components of the TME. The cells of the TME modify their surrounding cancer-characteristic ECM. This in turn provides feedback to them via cellular receptors, thereby regulating, together with cytokines and exosomes, differentiation processes as well as tumor progression and spread. Matrix remodeling is accomplished by altering the repertoire of ECM components and by biophysical changes in stiffness and tension caused by ECM-crosslinking and ECM-degrading enzymes, in particular matrix metalloproteinases (MMPs). These can degrade ECM barriers or, by partial proteolysis, release soluble ECM fragments called matrikines, which influence cells inside and outside the TME. This review examines the changes in the ECM of the TME and the interaction between cells and the ECM, with a particular focus on MMPs.

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Hyaluronan in the Tumor Microenvironment

Cited by 38 publications

References 152 publications

Oleate acid-stimulated HMMR expression by CEBPα is associated with nonalcoholic steatohepatitis and hepatocellular carcinoma

Oleate acid-stimulated HMMR expression by CEBPα is associated with nonalcoholic steatohepatitis and hepatocellular carcinoma

Hyaluronan Metabolism is Associated with DNA Repair Genes in Breast and Colorectal Cancer. Screening of Potential Progression Markers Using qPCR

Hold on or Cut? Integrin- and MMP-Mediated Cell–Matrix Interactions in the Tumor Microenvironment

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