Cadherin Expression, Vectorial Active Transport, and Metallothionein Isoform 3 Mediated EMT/MET Responses in Cultured Primary and Immortalized Human Proximal Tubule Cells

Slusser, Andrea; Bathula, Chandra S.; Sens, Donald A.; Somji, Seema; Sens, Mary Ann; Xu, Zhou; Garrett, Scott H.

doi:10.1371/journal.pone.0120132

Cited by 14 publications

(17 citation statements)

References 61 publications

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“…4a–c). The slight differences in the mobility of E-chaderin molecular species observed in western blot analysis are likely due to cell-specific post-translational modifications and/or to the occurence of alternative splicing (expression of different isoforms) as already reported in the literature24. These findings support the evidence that 1α-OH-vitD 3 impairs melanoma cell proliferation and triggers differentiation7.…”

Section: Resultssupporting

confidence: 84%

Antiproliferative Effects of 1α-OH-vitD3 in Malignant Melanoma: Potential Therapeutic implications

Spath¹,

Ulivieri

Lavra

et al. 2017

Sci Rep

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Early detection and surgery represent the mainstay of treatment for superficial melanoma, but for high risk lesions (Breslow’s thickness >0.75 mm) an effective adjuvant therapy is lacking. Vitamin D insufficiency plays a relevant role in cancer biology. The biological effects of 1α hydroxycholecalciferol on experimental melanoma models were investigated. 105 melanoma patients were checked for 25-hydroxycholecalciferol (circulating vitamin D) serum levels. Human derived melanoma cell lines and in vivo xenografts were used for studying 1α-hydroxycholecalciferol-mediated biological effects on cell proliferation and tumor growth. 99 out of 105 (94%) melanoma patients had insufficient 25-hydroxycholecalciferol serum levels. Interestingly among the six with vitamin D in the normal range, five had a diagnosis of in situ/microinvasive melanoma. Treatment with 1α-hydroxycholecalciferol induced antiproliferative effects on melanoma cells in vitro and in vivo, modulating the expression of cell cycle key regulatory molecules. Cell cycle arrest in G1 or G2 phase was invariably observed in vitamin D treated melanoma cells. The antiproliferative activity induced by 1α-hydroxycholecalciferol in experimental melanoma models, together with the discovery of insufficient 25-hydroxycholecalciferol serum levels in melanoma patients, provide the rationale for using vitamin D in melanoma adjuvant therapy, alone or in association with other therapeutic options.

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Section: Resultssupporting

confidence: 84%

Antiproliferative Effects of 1α-OH-vitD3 in Malignant Melanoma: Potential Therapeutic implications

Spath¹,

Ulivieri

Lavra

et al. 2017

Sci Rep

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“…The adherens junction cadherins (E-, P- and Ksp-cadherin) were either absent or expressed at a very low level in the HK-2 cells when compared to the HPT and the RPTEC/TERT1 cells. This data is in accord with a previous assessment of these proteins and the development of transepithelial resistance in HK-2 and HPT cells (Slusser et al, 2015 and Bathula et al, 2008). In addition to lacking E-cadherin, the HK-2 line highly expressed N-cadherin, a pattern commonly found in cells that have undergone a transition to a more mesenchymal morphology, also known as EMT.…”

Section: Discussionsupporting

confidence: 92%

“…While the transepithelial resistance of the cultured cells is still characteristic of a “leaky epithelium”, it is many fold higher than that measured in situ for the proximal tubule. Last, the expression of E-cadherin in the cultured cells appears to be elevated and N-cadherin reduced compared to that noted for the in situ proximal tubule (Nouwen et al 1993; Prozialeck et al 2004; Bathula et al 2008; Nurnberger et al 2010; Slusser et al 2015). Thus, primary cultures derived as described above from human renal cortex retain some, but not all, features of proximal tubule differentiation and will likely continue to be referred to as cultured HPT cells.…”

Section: Discussionmentioning

confidence: 75%

Human renal tubular cells contain CD24/CD133 progenitor cell populations: Implications for tubular regeneration after toxicant induced damage using cadmium as a model

Shrestha

Somji

Sens

et al. 2017

Toxicology and Applied Pharmacology

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The proximal tubules of the kidney are target sites of injury by various toxicants. Cadmium (Cd+2), an environmental nephrotoxicant can cause adverse effects and overt renal damage. To decipher the mechanisms involved in nephrotoxicity, an in vitro model system is required. Mortal cultures of human proximal tubule (HPT) cells have served, as models but are difficult to acquire and do not lend themselves to stable transfection. The immortalized human proximal tubule cell line HK-2, has served as a model but it lacks vectorial active transport and shows signs of lost epithelial features. Recently a new proximal tubule cell line was developed, the RPTEC/TERT1, and the goal of this study was to determine if this cell line could serve as a model to study nephrotoxicity. Global gene expression analysis of this cell line in comparison to the HK-2 and HPT cells showed that the RPTEC/TERT1 cells had gene expression patterns similar to HPT cells when compared to the HK-2 cells. The HPT and the RPTEC/TERT1 cell line had an increased population of stem/progenitor cells co-expressing CD24 and CD133 when compared to the HK-2 cells. The level of expression of cadherins, claudins and occludin molecules was also similar between the RPTEC/TERT1 and the HPT cells. Acute exposure to Cd+2 resulted in necrosis of the RPTEC/TERT1 cells when compared to the HK-2 cells which died by apoptosis. Thus, the RPTEC/TERT1 cells are similar to HPT cells and can serve as a good model system to study mechanisms involved in toxicant induced renal damage.

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“…β -Catenin is important for linkage of E-cadherins to the cytoskeleton [80, 81]. The downregulation of E-cadherin in carcinoma cells is associated with increased invasive ability of cancer cells [82, 83]. Furthermore, epithelial cell adhesion molecule (Ep-CAM) has been confirmed to be involved in tumor budding [84].…”

Section: Wnt/β-catenin Signal Pathway In Tumor Buddingmentioning

confidence: 99%

Tumor Budding, Micropapillary Pattern, and Polyploidy Giant Cancer Cells in Colorectal Cancer: Current Status and Future Prospects

Zhang¹,

Zhang²,

Yang³

et al. 2016

Stem Cells International

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We previously reported that polyploid giant cancer cells (PGCGs) induced by CoCl2 could form through endoreduplication or cell fusion. A single PGCC formed tumors in immunodeficient mice. PGCCs are also the key contributors to the cellular atypia and associate with the malignant grade of tumors. PGCCs have the properties of cancer stem cells and produce daughter cells via asymmetric cell division. Compared with diploid cancer cells, these daughter cells express less epithelial markers and acquire mesenchymal phenotype with importance in cancer development and progression. Tumor budding is generally recognized to correlate with a high recurrence rate, lymph node metastasis, chemoresistance, and poor prognosis of colorectal cancers (CRCs) and is a good indicator to predict the metastasis and aggressiveness in CRCs. Micropapillary pattern is a special morphologic pattern and also associates with tumor metastasis and poor prognosis. There are similar morphologic features and molecular phenotypes among tumor budding, micropapillary carcinoma pattern, and PGCCs with their budding daughter cells and all of them show strong ability of tumor invasion and migration. In this review, we discuss the cancer stem cell properties of PGCCs, the molecular mechanisms of their regulation, and the relationships with tumor budding and micropapillary pattern in CRCs.

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Cadherin Expression, Vectorial Active Transport, and Metallothionein Isoform 3 Mediated EMT/MET Responses in Cultured Primary and Immortalized Human Proximal Tubule Cells

Cited by 14 publications

References 61 publications

Antiproliferative Effects of 1α-OH-vitD3 in Malignant Melanoma: Potential Therapeutic implications

Antiproliferative Effects of 1α-OH-vitD3 in Malignant Melanoma: Potential Therapeutic implications

Human renal tubular cells contain CD24/CD133 progenitor cell populations: Implications for tubular regeneration after toxicant induced damage using cadmium as a model

Tumor Budding, Micropapillary Pattern, and Polyploidy Giant Cancer Cells in Colorectal Cancer: Current Status and Future Prospects

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