Hyaluronic acid synthase 2 promotes malignant phenotypes of colorectal cancer cells through transforming growth factor beta signaling

Kim, Young Heon; Lee, Seung Bum; Shim, Sehwan; Kim, Areumnuri; Park, Ji Hye; Jang, Won-Seok; Myung, Jae Kyung; Park, Sunhoo; Lee, Su Jae; Kim, Min Jung

doi:10.1111/cas.14070

Cited by 20 publications

(12 citation statements)

References 48 publications

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“…In fact, it has been shown that in many types of solid tumors, increased synthesis of HA by cancer cells or by tumor stromal cells is correlated with tumor growth and metastasis [ 9 , 142 ]. Recent studies have confirmed that the over-expression of HAS2 promotes tumor progression in breast, ovarian, bladder, colorectal, pancreatic and lung carcinoma and resistance to chemotherapy [ 143 , 144 , 145 , 146 , 147 , 148 ]. On the other hand, it was proved that inhibiting HA synthesis inhibits also metastasis of carcinoma cells in some types of tumors [ 144 , 149 ].…”

Section: Medical Applications Of Ha and Its Derivativesmentioning

confidence: 99%

Hyaluronic Acid: Redefining Its Role

Abatangelo

Vindigni

Avruscio

et al. 2020

Cells

243

166

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The discovery of several unexpected complex biological roles of hyaluronic acid (HA) has promoted new research impetus for biologists and, the clinical interest in several fields of medicine, such as ophthalmology, articular pathologies, cutaneous repair, skin remodeling, vascular prosthesis, adipose tissue engineering, nerve reconstruction and cancer therapy. In addition, the great potential of HA in medicine has stimulated the interest of pharmaceutical companies which, by means of new technologies can produce HA and several new derivatives in order to increase both the residence time in a variety of human tissues and the anti-inflammatory properties. Minor chemical modifications of the molecule, such as the esterification with benzyl alcohol (Hyaff-11® biomaterials), have made possible the production of water-insoluble polymers that have been manufactured in various forms: membranes, gauzes, nonwoven meshes, gels, tubes. All these biomaterials are used as wound-covering, anti-adhesive devices and as scaffolds for tissue engineering, such as epidermis, dermis, micro-vascularized skin, cartilage and bone. In this review, the essential biological functions of HA and the applications of its derivatives for pharmaceutical and tissue regeneration purposes are reviewed.

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Section: Medical Applications Of Ha and Its Derivativesmentioning

confidence: 99%

Hyaluronic Acid: Redefining Its Role

Abatangelo

Vindigni

Avruscio

et al. 2020

Cells

243

166

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“…Hyaluronan synthases 2 (HAS2), a member of hyaluronan synthesis family, forms and synthesizes of hyaluronan. Hyaluronan, together with its cell surface receptors, has been shown to contribute to cancer development such as cell migration and invasion [ 10 , 11 ]. HAS2 has been reported to be correlated with the cancer grade and survival of breast cancer patients [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Increased SPHK1 and HAS2 Expressions Correlate to Poor Prognosis in Pancreatic Cancer

Zhang

Wang³

et al. 2021

BioMed Research International

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Objective. SPHK1 and HAS2 have been reported to play important roles in tumorigenesis and development. However, their expression and prognostic value in pancreatic cancer (PC) remain unclear. This study is aimed at investigating the expression of SPHK1 and HAS2 on the prognosis of pancreatic cancer. Materials and Methods. The expression of SPHK1 and HAS2 in pancreatic cancer tissues was analyzed through TCGA and GTEx databases and validated by qRT-PCR and Western blot in pancreatic cancer cell lines. χ 2 test was used to explore the correlation of the SPHK1 and HAS2 expressions with clinical characteristics. Kaplan-Meier survival analysis and ROC curve were used to evaluate the prognostic and diagnostic roles of SPHK1 and HAS2 in pancreatic cancer. Additionally, Spearman correlation analysis was applied to assess the correlation between the SPHK1 and HAS2 in pancreatic cancer. GO analysis and KEGG analysis were applied to explore the possible signaling pathway that SPHK1 and HAS2 coregulated genes mediated. Results. The expression of SPHK1 and HAS2 was markedly upregulated in pancreatic cancer tissue and cell lines, respectively. Furthermore, there was a significant positive correlation between SPHK1 and HAS2 expressions. ROC curves showed that SPHK1 combine with HAS2 has good diagnostic value in pancreatic cancer patients with 85% sensitivity and 99.4% specificity. Kaplan-Meier analysis showed that increased expression of SPHK1 and HAS2 was significantly associated with short overall survival (OS) of pancreatic cancer patients. GO and KEGG results revealed that SPHK1 and HAS2 mainly involved cell proliferation and invasion mediated by extracellular matrix- (ECM-) receptor interaction, focal adhesion, and PI3K-AKT signaling pathways. Conclusions. Overexpression of SPHK1 and HAS2 could be important markers for the prognosis of pancreatic cancer.

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“…It provides cells with structural support, allowing for cell proliferation, growth and migration to take place [ 53 ]. The main components of ECM include structural proteins such as collagen, fibronectin, laminin, proteoglycans and hyaluronic acid [ 53 , 89 , 90 , 91 , 92 ]. The ECM also contains a variety of cytokines and growth factors which can affect the initiation and progression of CRC [ 93 ].…”

Section: Tumor Microenvironmentmentioning

confidence: 99%

A 3D View of Colorectal Cancer Models in Predicting Therapeutic Responses and Resistance

Reidy

Leonard

Treacy

et al. 2021

Cancers

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Although there have been many advances in recent years for the treatment of colorectal cancer (CRC), it still remains the third most common cause of cancer-related deaths worldwide. Many patients with late stage CRC display resistance to multiple different therapeutics. An important aspect in developing effective therapeutics for CRC patients is understanding the interactions that take place in the tumor microenvironment (TME), as it has been shown to contribute to drug resistance in vivo. Much research over the past 100 years has focused on 2D monolayer cultures or in vivo studies, however, the efficacy in translating these to the clinic is very low. More recent studies are turning towards developing an effective 3D model of CRC that is clinically relevant, that can recapitulate the TME in vitro and bridge the gap between 2D cultures and in vivo studies, with the aim of reducing the use of animal models in the future. This review summarises the advantages and limitations of different 3D CRC models. It emphasizes how different 3D models may be optimised to study cellular and extracellular interactions that take place in the TME of CRC in an effort to allow the development of more translatable effective treatment options for patients.

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Hyaluronic acid synthase 2 promotes malignant phenotypes of colorectal cancer cells through transforming growth factor beta signaling

Cited by 20 publications

References 48 publications

Hyaluronic Acid: Redefining Its Role

Hyaluronic Acid: Redefining Its Role

Increased SPHK1 and HAS2 Expressions Correlate to Poor Prognosis in Pancreatic Cancer

A 3D View of Colorectal Cancer Models in Predicting Therapeutic Responses and Resistance

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