Sugars in the microenvironment: the sticky problem of HA turnover in tumors

Schmaus, Anja; Jochen, Bauer; Sleeman, Jonathan

doi:10.1007/s10555-014-9532-2

Cited by 40 publications

(44 citation statements)

References 219 publications

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“…Based on these findings we hypothesized that digested, small fragments of HA (in the range of <30 kDa) still remained in FbECM and FbColl, since HYAL1 degrade HA into HA fragments in the range of 20 kDa 53 to 66 kDa. 54 Furthermore, it has to be recognized, that the small HA fragments cannot be detected with the HA-ELISA kit used here or with HA-binding proteins. 55 Since Ctrl matrices contained higher amounts of HA than Has2-KD matrices, it can be assumed that more LMW-HA fragments were present after HYAL treatment, and in turn, could have led to an increased response of melanoma cells.…”

Section: Biomaterials Science Papermentioning

confidence: 99%

Biomimetic tissue models reveal the role of hyaluronan in melanoma proliferation and invasion

et al. 2020

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Section: Biomaterials Science Papermentioning

confidence: 99%

Biomimetic tissue models reveal the role of hyaluronan in melanoma proliferation and invasion

et al. 2020

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“…Cancer development and progression including initiation, proliferation, invasion, metastasis and therapeutic resistance are driven by increasingly accumulated genetic and epigenetic alterations in cancer cells themselves as well as constructional changes in their microenvironment (8). Stromal cells and the ECM of the microenvironment can serve as a significant regulator of cancer initiation, growth and progression (9,10). Fifteen…”

Section: Introductionmentioning

confidence: 99%

Effect of evodiamine and berberine on the interaction between DNMTs and target microRNAs during malignant transformation of the colon by TGF-β1

et al. 2017

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The tissue microenvironment functions as a crucial player in carcinogenesis, and transforming growth factor-β1 (TGF-β1) within the microenvironment stimulates the formation of neoplasms. Using an in vitro model of malignancy induced by TGF-β1, we assessed the effect of evodiamine and berberine on the interaction between DNA methyltransferases (DNMTs) and target microRNAs (miRNAs) in the model. Colon tissues from neonatal rats 7 days of age were cultured and malignancy was induced by TGF-β1 in vitro for 48 h, and then the tissues were respectively treated with evodiamine and berberine for 24 h. Morphological alteration of tissues was observed by an inverted microscope, histological structures were observed using hematoxylin and eosin staining, and the expression levels of DNMTs and targeted miRNAs screened by bioinformatics software combined with Gene chip analysis in our previous study were detected by immunohistochemistry and quantified by real-time PCR. Twenty-four hours after treatment with TGF-β1, expression levels of DNMT1, DNMT3A, DNMT3B and miR-152 (target DNMT1), miR-429 (target DNMT3A) and miR-29a (target DNMT3A/3B) were markedly decreased; however, after 48 h, the expression levels of DNMT1 and DNMT3A were significantly increased, but their target miRNAs were still decreased. After treatment with a DNMT inhibitor (5-Aza-dC), expression levels of the miRNAs were increased to a larger extent, but did not reach normal levels. After treatment with berberine and evodiamine for 24 h, respectively, increased expression of DNMT1, DNMT3A, DNMT3B and miR-152, miR-429, miR-29a was noted. In conclusion, the results of the present study suggest that miRNAs can also be post-transcriptionally regulated by their corresponding DNMTs and that berberine and evodiamine regulate the expression of these genes, which provides early epigenetic evidence for the prevention and therapy of colorectal cancer.

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“…HA is synthesized as a high molecular weight polymer of up to 10 7 Da (HMW-HA), but during tissue injury and inflammation, enhanced synthesis combined with cleavage of HA, for example through the activities of hyaluronidases and free radicals, can result in HA fragmentation and the accumulation of HA oligosaccharides [33–38]. Ionizing irradiation can also fragment HA directly [39].…”

Section: Introductionmentioning

confidence: 99%

TGF-β1 Is Present at High Levels in Wound Fluid from Breast Cancer Patients Immediately Post-Surgery, and Is Not Increased by Intraoperative Radiation Therapy (IORT)

et al. 2016

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In patients with low-risk breast cancer, intraoperative radiotherapy (IORT) during breast-conserving surgery is a novel and convenient treatment option for delivering a single high dose of irradiation directly to the tumour bed. However, edema and fibrosis can develop after surgery and radiotherapy, which can subsequently impair quality of life. TGF- β is a strong inducer of the extracellular matrix component hyaluronan (HA). TGF-β expression and HA metabolism can be modulated by irradiation experimentally, and are involved in edema and fibrosis. We therefore hypothesized that IORT may regulate these factors.Wound fluid (WF) draining from breast lumpectomy sites was collected and levels of TGF-β1 and HA were determined by ELISA. Proliferation and marker expression was analyzed in primary lymphatic endothelial cells (LECs) treated with recombinant TGF-β or WF. Our results show that IORT does not change TGF-β1 or HA levels in wound fluid draining from breast lumpectomy sites, and does not lead to accumulation of sHA oligosaccharides. Nevertheless, concentrations of TGF-β1 were high in WF from patients regardless of IORT, at concentrations well above those associated with fibrosis and the suppression of LEC identity. Consistently, we found that TGF-β in WF is active and inhibits LEC proliferation. Furthermore, all three TGF-β isoforms inhibited LEC proliferation and suppressed LEC marker expression at pathophysiologically relevant concentrations.Given that TGF-β contributes to edema and plays a role in the regulation of LEC identity, we suggest that inhibition of TGF-β directly after surgery might prevent the development of side effects such as edema and fibrosis.

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Sugars in the microenvironment: the sticky problem of HA turnover in tumors

Cited by 40 publications

References 219 publications

Biomimetic tissue models reveal the role of hyaluronan in melanoma proliferation and invasion

Biomimetic tissue models reveal the role of hyaluronan in melanoma proliferation and invasion

Effect of evodiamine and berberine on the interaction between DNMTs and target microRNAs during malignant transformation of the colon by TGF-β1

TGF-β1 Is Present at High Levels in Wound Fluid from Breast Cancer Patients Immediately Post-Surgery, and Is Not Increased by Intraoperative Radiation Therapy (IORT)

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