Unique angiogenic and vasculogenic properties of renal cell carcinoma in a xenograft model of bone metastasis are associated with high levels of <i>vegf‐a</i> and decreased <i>ang‐1</i> expression

Xie, Chao; Schwarz, Edward M.; Sampson, Erik R.; Dhillon, Robinder S.; Li, Dan; O’Keefe, Regis J.; Tyler, Wakenda

doi:10.1002/jor.21500

Cited by 24 publications

(26 citation statements)

References 37 publications

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“…These cells produce high levels of VEGF [46] as well, which is characteristic of ccRCC. This cell line can be used to model bone metastasis in RCC- 786-O cells injected into nude mice, both directly to the tibia or to the cardiac ventricle, cause bone destruction and vascularization [62, 63]. A subline derived from such metastatic tumors can be cultured in vitro in 3D systems that retain bone metastasis characteristics [64].…”

Section: Introductionmentioning

confidence: 99%

Choosing the right cell line for renal cell cancer research

Brodaczewska¹,

Szczylik²,

et al. 2016

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Cell lines are still a tool of choice for many fields of biomedical research, including oncology. Although cancer is a very complex disease, many discoveries have been made using monocultures of established cell lines. Therefore, the proper use of in vitro models is crucial to enhance our understanding of cancer. Therapeutics against renal cell cancer (RCC) are also screened with the use of cell lines. Multiple RCC in vitro cultures are available, allowing in vivo heterogeneity in the laboratory, but at the same time, these can be a source of errors. In this review, we tried to sum up the data on the RCC cell lines used currently. An increasing amount of data on RCC shed new light on the molecular background of the disease; however, it revealed how much still needs to be done. As new types of RCC are being distinguished, novel cell lines and the re-exploration of old ones seems to be indispensable to create effective in vitro tools for drug screening and more.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-016-0565-8) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Choosing the right cell line for renal cell cancer research

Brodaczewska¹,

Szczylik²,

et al. 2016

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“…Angiogenesis is required, and studies have confirmed that hypervascularity is commonly associated with RCC [6], [7]. The loss of the von Hippel-Lindau (VHL) tumor suppressor gene in most of RCCs leads to constitutive activation of hypoxia-inducible factor-1α (HIF-1α), resulting in the induction of multiple pro-angiogenic molecules such as vascular endothelial growth factor (VEGF) [7], [20], [21].…”

Section: Introductionmentioning

confidence: 99%

Cadherin-11 in Renal Cell Carcinoma Bone Metastasis

et al. 2014

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Bone is one of the common sites of metastases from renal cell carcinoma (RCC), however the mechanism by which RCC preferentially metastasize to bone is poorly understood. Homing/retention of RCC cells to bone and subsequent proliferation are necessary steps for RCC cells to colonize bone. To explore possible mechanisms by which these processes occur, we used an in vivo metastasis model in which 786-O RCC cells were injected into SCID mice intracardially, and organotropic cell lines from bone, liver, and lymph node were selected. The expression of molecules affecting cell adhesion, angiogenesis, and osteolysis were then examined in these selected cells. Cadherin-11, a mesenchymal cadherin mainly expressed in osteoblasts, was significantly increased on the cell surface in bone metastasis-derived 786-O cells (Bo-786-O) compared to parental, liver, or lymph node-derived cells. In contrast, the homing receptor CXCR4 was equivalently expressed in cells derived from all organs. No significant difference was observed in the expression of angiogenic factors, including HIF-1α, VEGF, angiopoeitin-1, Tie2, c-MET, and osteolytic factors, including PTHrP, IL-6 and RANKL. While the parental and Bo-786-O cells have similar proliferation rates, Bo-786-O cells showed an increase in migration compared to the parental 786-O cells. Knockdown of Cadherin-11 using shRNA reduced the rate of migration in Bo-786-O cells, suggesting that Cadherin-11 contributes to the increased migration observed in bone-derived cells. Immunohistochemical analysis of cadherin-11 expression in a human renal carcinoma tissue array showed that the number of human specimens with positive cadherin-11 activity was significantly higher in tumors that metastasized to bone than that in primary tumors. Together, these results suggest that Cadherin-11 may play a role in RCC bone metastasis.

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“…We report that bone-derived 786-O RCC cells grow as spheroids in a 3D HA-based hydrogel system with a decreased proliferative capacity as compared to cells cultured on 2D, which grow as a monolayer. The transition from 2D to 3D culture resulted in phenotypic changes that are consistent with the characteristics of RCC bone metastases in patients, such as hypervascularity [23,24] and osteolysis [4,5]. Based on these observations, we conclude that 3D HA-based hydrogels may enable more accurate studies of RCC bone metastasis in vitro as compared to traditional 2D models and is a more suitable in vitro model for screening drugs for the treatment of bone metastatic RCC.…”

Section: Discussionmentioning

confidence: 60%

Three-dimensional (3D) culture of bone-derived human 786-O renal cell carcinoma retains relevant clinical characteristics of bone metastases

et al. 2015

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Bone metastases from renal cell carcinoma (RCC) are typically lytic, destructive, and resistant to treatment regimens. Current in vitro models for studying metastasis introduce artifacts that limit their usefulness. Many features of tumors growing in bone are lost when human RCC cells are cultured in two-dimensional (2D) plastic substrata. In this study, we established that RCC spheroids, consisting of aggregates of cells, can be grown in a three-dimensional (3D) hyaluronate hydrogel-based culture system. The bone-derived human 786-O RCC subline proliferated and survived long term in these hydrogels. Additionally, RCC spheroids in 3D hydrogels demonstrated lower proliferation rates than their counterparts grown in 2D. Overall, gene expression patterns of RCC spheroids in 3D more closely mimicked those observed in vivo than did those of cells grown in 2D. Of particular importance, selected adhesion molecules, angiogenesis factors and osteolytic factors that have been shown to be involved in RCC bone metastasis were found to be expressed at higher levels in 3D than in 2D cultures. We propose that the 3D culture system provides an improved platform for RCC bone metastasis studies compared with 2D systems.

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Unique angiogenic and vasculogenic properties of renal cell carcinoma in a xenograft model of bone metastasis are associated with high levels of vegf‐a and decreased ang‐1 expression

Cited by 24 publications

References 37 publications

Choosing the right cell line for renal cell cancer research

Choosing the right cell line for renal cell cancer research

Cadherin-11 in Renal Cell Carcinoma Bone Metastasis

Three-dimensional (3D) culture of bone-derived human 786-O renal cell carcinoma retains relevant clinical characteristics of bone metastases

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