A guide to hyaluronan and related enzymes in breast cancer: biological significance and diagnostic value

Velesiotis, Christos; Vasileiou, Stella; Vynios, Demitrios H.

doi:10.1111/febs.14860

Cited by 22 publications

(20 citation statements)

References 103 publications

(163 reference statements)

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“…The EP protocol for both 2D and 3D cell cultures was performed using two different types of electrodes ( Supplementary Figure S1), i.e., a plate and a linear electrode, and applying 8 voltage pulses (1300 V/cm, 100 µs long at 1 Hz), as reported in [39]. The plate electrode was formed by two 3 cm long, 1 cm large stainless-steel plates, with a gap of 7 mm, while the linear electrode was formed by a set of 8 needles organized in 2 parallel lines at 4 mm.…”

Section: Get Protocols On 2d Vs 3d Cell Culturesmentioning

confidence: 99%

“…On the other hand, overproduction of other ECM components like fibronectin heparan sulfate, proteoglycans, and hyaluronic acid plays a significant role in breast cancer progression and metastasis [38]. In particular, hyaluronic acid is a unique nonsulfated glycosaminoglycan that is overexpressed in breast cancer and contributes to cancer cell growth and functional properties [39].…”

Section: Introductionmentioning

confidence: 99%

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The Efficiency of Gene Electrotransfer in Breast-Cancer Cell Lines Cultured on a Novel Collagen-Free 3D Scaffold

Sieni

Dettin

Robertis

et al. 2020

Cancers

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Gene Electro-Transfer (GET) is a powerful method of DNA delivery with great potential for medical applications. Although GET has been extensively studied in vitro and in vivo, the optimal parameters remain controversial. 2D cell cultures have been widely used to investigate GET protocols, but have intrinsic limitations, whereas 3D cultures may represent a more reliable model thanks to the capacity of reproducing the tumor architecture. Here we applied two GET protocols, using a plate or linear electrode, on 3D-cultured HCC1954 and MDA-MB231 breast cancer cell lines grown on a novel collagen-free 3D scaffold and compared results with conventional 2D cultures. To evaluate the electrotransfer efficiency, we used the plasmid pEGFP-C3 encoding the enhanced green fluorescent protein (EGFP) reporter gene. The novel 3D scaffold promoted extracellular matrix deposition, which particularly influences cell behavior in both in vitro cell cultures and in vivo tumor tissue. While the transfection efficiency was similar in the 2D-cultures, we observed significant differences in the 3D-model. The transfection efficiency in the 3D vs 2D model was 44% versus 15% (p < 0.01) and 24% versus 17% (p < 0.01) in HCC1954 and MDA-MB231 cell cultures, respectively. These findings suggest that the novel 3D scaffold allows reproducing, at least partially, the peculiar morphology of the original tumor tissues, thus allowing us to detect meaningful differences between the two cell lines. Following GET with plate electrodes, cell viability was higher in 3D-cultured HCC1954 (66%) and MDA-MB231 (96%) cell lines compared to their 2D counterpart (53% and 63%, respectively, p < 0.001). Based on these results, we propose the novel 3D scaffold as a reliable support for the preparation of cell cultures in GET studies. It may increase the reliability of in vitro assays and allow the optimization of GET parameters of in vivo protocols.

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Section: Get Protocols On 2d Vs 3d Cell Culturesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Efficiency of Gene Electrotransfer in Breast-Cancer Cell Lines Cultured on a Novel Collagen-Free 3D Scaffold

Sieni

Dettin

Robertis

et al. 2020

Cancers

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“…The content of hyaluronic acid is low in normal breast tissue, but in 56% of breast cancer cases, high levels of HA are found in malignant epithelium and peritumoral stroma [42,43]. Taking into account that the increased HA accumulation, especially in the tumor stroma, signals the metastatic dissemination of cancer, as well as the poor prognosis, the effect of the major receptor of HA, CD44, its isoform and its variants, and the synthases of HA was investigated in breast cancer cell lines of different estrogen receptor status.…”

Section: Lumican Affects the Expression Levels Of Invadopodia Markersmentioning

confidence: 99%

Evaluation of lumican effects on morphology of invading breast cancer cells, expression of integrins and downstream signaling

et al. 2020

Self Cite

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The small leucine-rich proteoglycan lumican regulates estrogen receptors (ERs)-associated functional properties of breast cancer cells, expression of matrix macromolecules, and epithelial-to-mesenchymal transition. However, it is not known whether the ER-dependent lumican effects on breast cancer cells are related to the expression of integrins and their intracellular signaling pathways. Here, we analyzed the effects of lumican in three breast cancer cell lines: the highly metastatic ERb-positive MDA-MB-231, cells with the respective ERb-suppressed (shERbMDA-MB-231), and lowly invasive ERa-positive MCF-7/c breast cancer cells. Scanning electron microscopy, confocal microscopy, real-time PCR, western blot, and cell adhesion assays were performed. Lumican effects on breast cancer cell morphology were also investigated in 3-dimensional collagen cultures. Lumican treatment induced cell-cell contacts and cell grouping and inhibited microvesicles and microvilli formation. The expression of the cell surface adhesion receptor CD44, its isoform and variants, hyaluronan (HA), and HA synthases was also investigated. Lumican inhibited the expression of CD44 and HA synthases, and its effect on cell adhesion revealed a major role of a1, a2, a3, aVb3, and aVb5 integrins in MDA-MB-231 cells, but not in MCF-7/c cells. Lumican upregulated the expression of a2 and b1 integrin subunits both in MDA-MB-231 and in shERbMDA-MB-231 as compared to MCF-7/c cells. Downstream signaling pathways for integrins, such as FAK, ERK 1/2 MAPK 42/44, and Akt, were found to be downregulated by lumican. Our data shed light to the molecular mechanisms responsible for the anticancer activity of lumican in invasive breast cancer.

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“…It is well known that HA levels are usually increased in many solid tumors, such as colorectal, prostate, and breast cancer 23 – 25 . A clinical survey has proved a close correlation between high-stromal HA enrichment and poor survival in breast cancer patients 26 , 27 .…”

Section: Introductionmentioning

confidence: 99%

Reduced hyaluronan cross-linking induces breast cancer malignancy in a CAF-dependent manner

Zhang

Liu

et al. 2021

Cell Death Dis

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Hyaluronan (HA) cross-linking is a conformational state of HA, a covalent complex between HA and heavy chains (HCs) from inter-α-trypsin inhibitor (I-α-I) mediated by tumor necrosis factor-induced protein 6 (TSG6). Cross-linked HA has been identified as a protective factor in physiological and inflammatory conditions. However, the state of HA cross-linking in tumor microenvironment has not been fully elucidated. As a major constituent of the extracellular matrix (ECM), HA is mainly synthesized by cancer-associated fibroblasts (CAFs). Our study aimed to clarify the role of HA cross-linking in breast cancer malignancy. Compared to normal mammary gland tissues, cross-linked HA levels were significantly decreased in breast cancer and associated with tumor malignancy. When NFbs were activated into CAFs, the levels of cross-linked HA and TSG6 were both suppressed. Through upregulating TSG6, CAFs restored the high level of cross-linked HA and significantly inhibited breast cancer malignancy, whereas NFbs promoted the malignancy when the cross-linked HA level was reduced. Furthermore, the inhibitory role of HA cross-linking in tumor malignancy was directly verified using the synthesized HA-HC complex. Collectively, our study found that the deficiency of cross-linked HA induced breast cancer malignancy in a CAF-dependent manner, suggesting that recovering HA cross-linking may be a potential therapeutic strategy.

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A guide to hyaluronan and related enzymes in breast cancer: biological significance and diagnostic value

Cited by 22 publications

References 103 publications

The Efficiency of Gene Electrotransfer in Breast-Cancer Cell Lines Cultured on a Novel Collagen-Free 3D Scaffold

The Efficiency of Gene Electrotransfer in Breast-Cancer Cell Lines Cultured on a Novel Collagen-Free 3D Scaffold

Evaluation of lumican effects on morphology of invading breast cancer cells, expression of integrins and downstream signaling

Reduced hyaluronan cross-linking induces breast cancer malignancy in a CAF-dependent manner

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