Targeting RNF8 Effectively Reverse Cisplatin and Doxorubicin Resistance in Endometrial Cancer

2020 ◽  
Author(s):  
Ben Yang ◽  
Wang Ke ◽  
Yingchun Wan ◽  
Tao Li
Keyword(s):  
Endometrial Cancer ◽  
Cell Lines ◽  
Quantitative Polymerase Chain Reaction ◽  
Mrna Levels ◽  
Mice Model ◽  
Expression Levels ◽  
Gynecological Malignancy ◽  
Ec Cells

Abstract Background Endometrial cancer (EC) is one of the most frequent gynecological malignancy worldwide. However, resistance to chemotherapy remains one of the major difficulties in the treatment of EC. Thus, there is an urgent requirement to understand mechanisms of chemoresistance and identify novel regimens for patients with EC. Methods Cisplatin and doxorubicin resistant cell lines were acquired by continuous exposing parental EC cells to cisplatin or doxorubicin for 3 months. Cell viability was determined by using MTT assay. Protein Expression levels of protein were examined by western blotting assay. mRNA levels were measured by quantitative polymerase chain reaction (qPCR) assay. Ring finger protein 8 (RNF8) knockout cell lines were generated by clustered regularly interspaced short palindromic repeats (CRISPR)–Cas9 gene editing assay. Nonhomologous end joining (NHEJ) efficiency were quantified by plasmid based NHEJ assay. DNA double strand breaks (DSB) were generated using laser micro-irradiation. Protein recruitment to DSB was analyzed by immunofluorescent assay. Tumor growth was examined by AN3CA xenograft mice model. Results We found that protein and mRNA expression levels of RNF8 were significantly increased in both cisplatin and doxorubicin resistant EC cells. Cell survival assay showed that RNF deficiency significantly enhanced the sensitivity of resistant EC cells to cisplatin and doxorubicin (P < 0.01). In addition, chemoresistant EC cells exhibited increased NHEJ efficiency. Knockout of RNF8 in chemoresistant EC cells significantly reduced NHEJ efficiency and prolonged Ku80 retention on DSB. Moreover, cisplatin resistant AN3CA xenograft showed that RNF8 deficiency overcame cisplatin resistance. Conclusions Our in vitro and in vivo assays provide evidence for RNF8, which is a NHEJ factor, serving as a promising, novel target in EC chemotherapy.

scholarly journals Tribbles Pseudokinase 3 Contributes to Cancer Stemness of Endometrial Cancer Cells by Regulating β-Catenin Expression

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3785
Author(s):  
Wen-Ling Wang ◽  
Guan-Ci Hong ◽  
Peng-Ju Chien ◽  
Yu-Hao Huang ◽  
Hsueh-Te Lee ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Messenger Rna ◽  
Tumor Development ◽  
The Cancer Genome Atlas ◽  
Scaffolding Protein ◽  
Mrna Levels ◽  
Cancer Stemness ◽  
Gynecological Malignancy ◽  
Ec Cells

Endometrial cancer (EC) is the second most common gynecological malignancy worldwide. Tribbles pseudokinase 3 (TRIB3) is a scaffolding protein that regulates intracellular signal transduction, and its role in tumor development is controversial. Here, we investigated the biological function of TRIB3 in EC. We found that the messenger RNA (mRNA) expression level of TRIB3 was significantly and positively correlated with shorter overall survival of EC patients in The Cancer Genome Atlas database. The protein expression of TRIB3 was found to be significantly increased in EC cancer stem cells (CSCs) enriched by tumorsphere cultivation. Knockdown of TRIB3 in EC cells suppressed tumorsphere formation, the expression of cancer stemness genes, and the in vivo tumorigenesis. The expression of β-catenin at both the protein and the mRNA levels was downregulated upon TRIB3 silencing. TRIB3 was found to interact with E74 Like ETS transcription factor 4 (ELF4) in the nucleus and bound to ELF4 consensus sites within the catenin beta 1 (CTNNB1) promoter in EC cell lines. These data indicated that TRIB3 may regulate CTNNB1 transcription by enhancing the recruitment of ELF4 to the CTNNB1 promoter. In conclusion, our results suggest that TRIB3 plays an oncogenic role in EC and positively regulates the self-renewal and tumorigenicity of EC-CSCs. Targeting TRIB3 is considered as a potential therapeutic strategy in future EC therapy.

scholarly journals Assessing Estrogen-Induced Proliferative Response in an Endometrial Cancer Cell Line Using a Universally Applicable Methodological Guide

2018 ◽  
Vol 28 (1) ◽  
pp. 122-133 ◽  
Author(s):  
Christina Parkes ◽  
Areege Kamal ◽  
Anthony J. Valentijn ◽  
Rafah Alnafakh ◽  
Stephane R. Gross ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Proliferative Response ◽  
Quantitative Polymerase Chain Reaction ◽  
Chorioallantoic Membrane ◽  
Tumor Formation ◽  
Membrane Model

ObjectiveTranslational endometrial cancer (EC) research benefits from an in vitro experimental approach using EC cell lines. We demonstrated the steps that are required to examine estrogen-induced proliferative response, a simple yet important research question pertinent to EC, and devised a pragmatic methodological workflow for using EC cell lines in experimental models.MethodsComprehensive review of all commercially available EC cell lines was carried out, and Ishikawa cell line was selected to study the estrogen responsiveness with HEC1A, RL95-2, and MFE280 cell lines as comparators where appropriate, examining relevant differential molecular (steroid receptors) and functional (phenotype, anchorage-independent growth, hormone responsiveness, migration, invasion, and chemosensitivity) characteristics in 2-dimensional and 3-dimensional cultures in vitro using immunocytochemistry, immunofluorescence, quantitative polymerase chain reaction, and Western blotting. In vivo tumor, formation, and chemosensitivity were also assessed in a chick chorioallantoic membrane model.ResultsShort tandem repeat analysis authenticated the purchased cell lines, whereas gifted cells deviated significantly from the published profile. We demonstrate the importance of prior assessment of the suitability of each cell line for the chosen in vitro experimental technique. Prior establishment of baseline, nonenriched conditions was required to induce a proliferative response to estrogen. The chorioallantoic membrane model was a suitable in vivo multicellular animal model for EC for producing rapid and reproducible data.ConclusionsWe have developed a methodological guide for EC researchers when using endometrial cell lines to answer important translational research questions (exemplified by estrogen-responsive cell proliferation) to facilitate robust data, while saving time and resources.

scholarly journals TRIM27 interacts with Iκbα to promote the growth of human renal cancer cells through regulating the NF-κB pathway

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chengwu Xiao ◽  
Wei Zhang ◽  
Meimian Hua ◽  
Huan Chen ◽  
Bin Yang ◽  
...  
Keyword(s):  
Cell Lines ◽  
Prognostic Indicator ◽  
The Cancer Genome Atlas ◽  
Mrna Levels ◽  
Loss Of Function ◽  
Protein Levels ◽  
Kaplan Meier ◽  
Cancer Genome Atlas

Abstract Background The tripartite motif (TRIM) family proteins exhibit oncogenic roles in various cancers. The roles of TRIM27, a member of the TRIM super family, in renal cell carcinoma (RCC) remained unexplored. In the current study, we aimed to investigate the clinical impact and roles of TRIM27 in the development of RCC. Methods The mRNA levels of TRIM27 and Kaplan–Meier survival of RCC were analyzed from The Cancer Genome Atlas database. Real-time PCR and Western blotting were used to measure the mRNA and protein levels of TRIM27 both in vivo and in vitro. siRNA and TRIM27 were exogenously overexpressed in RCC cell lines to manipulate TRIM27 expression. Results We discovered that TRIM27 was elevated in RCC patients, and the expression of TRIM27 was closely correlated with poor prognosis. The loss of function and gain of function results illustrated that TRIM27 promotes cell proliferation and inhibits apoptosis in RCC cell lines. Furthermore, TRIM27 expression was positively associated with NF-κB expression in patients with RCC. Blocking the activity of NF-κB attenuated the TRIM27-mediated enhancement of proliferation and inhibition of apoptosis. TRIM27 directly interacted with Iκbα, an inhibitor of NF-κB, to promote its ubiquitination, and the inhibitory effects of TRIM27 on Iκbα led to NF-κB activation. Conclusions Our results suggest that TRIM27 exhibits an oncogenic role in RCC by regulating NF-κB signaling. TRIM27 serves as a specific prognostic indicator for RCC, and strategies targeting the suppression of TRIM27 function may shed light on future therapeutic approaches.

scholarly journals Nuclear upregulation of PI3K p110β correlates with increased rRNA transcription in endometrial cancer cells

2019 ◽  
Author(s):  
Fatemeh Mazloumi Gavgani ◽  
Thomas Karlsson ◽  
Ingvild L Tangen ◽  
Andrea Papdiné Morovicz ◽  
Victoria Smith Arnesen ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Pi3k Pathway ◽  
Clinical Samples ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Cytoplasmic Staining ◽  
Ec Cells

AbstractGenes encoding for components of the phosphoinositide 3-kinase (PI3K) pathway are frequently mutated in cancer, including inactivating mutations of PTEN and activating mutations of PIK3CA, encoding the PI3K catalytic subunit p110α. PIK3CB, encoding p110β, is rarely mutated, but can contribute to tumourigenesis in some PTEN-deficient tumours. The underlying molecular mechanisms are however poorly understood. By analysing cell lines and annotated clinical samples, we have previously found that p110β is highly expressed in endometrial cancer (EC) cell lines and that PIK3CB mRNA levels increase early in primary tumours correlating with lower survival. Selective inhibition of p110α and p110β led to different effects on cell signalling and cell function, p110α activity being correlated to cell survival in PIK3CA mutant cells and p110β with cell proliferation in PTEN-deficient cells. To understand the mechanisms governing the differential roles of these isoforms, we assessed their sub-cellular localisation. p110α was cytoplasmic whereas p110β was both cytoplasmic and nuclear with increased levels in both compartments in cancer cells. Immunohistochemistry of p110β in clinically annotated patient tumour sections revealed high nuclear/cytoplasmic staining ratio, which correlated significantly with higher grades. Consistently, the presence of high levels of p110β in the nuclei of EC cells, correlated with high levels of its product phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) in the nucleus. Using immunofluorescence labelling, we observed both p110β and PtdIns(3,4,5)P3 in the nucleoli of EC cell lines. The production of nucleolar PtdIns(3,4,5)P3 was dependent upon p110β activity. EC cells with high levels of nuclear PtdIns(3,4,5)P3 and p110β showed elevated nucleolar activity as assessed by the increase in 47S pre-rRNA transcriptional levels in a p110β-dependent manner. Altogether, these results present a nucleolar role for the PI3K pathway that may contribute to tumour progression in endometrial cancer.

scholarly journals Overexpression of cyclin D1 in the Dami megakaryocytic cell line causes growth arrest

Blood ◽  
1995 ◽  
Vol 86 (1) ◽  
pp. 294-304 ◽  
Author(s):  
CC Wilhide ◽  
C Van Dang ◽  
J Dipersio ◽  
AA Kenedy ◽  
PF Bray
Keyword(s):  
Cyclin D1 ◽  
Cell Line ◽  
Cell Lines ◽  
Northern Blotting ◽  
Mrna Levels ◽  
Cyclin Dependent Kinases ◽  
Megakaryocyte Differentiation ◽  
Megakaryocytic Cell

The maturation of megakaryocytes in vivo requires polyploidization or repeated duplication of DNA without cytokinesis. As DNA replication and cytokinesis are tightly regulated in somatic cells by cyclins and cyclin-dependent kinases, we sought to determine the pattern of cyclin gene expression in cells that undergo megakaryocytic differentiation and polyploidization. The Dami megakaryocytic cell line differentiates and increases ploidy in response to phorbol 12-myristate 13-acetate (PMA) stimulation in vitro. We used Northern blotting to analyze mRNA levels of cyclins A, B, C, D1, and E in PMA-induced Dami cells and found that cyclin D1 mRNA levels increased dramatically (18-fold). Similar increases in cyclin D1 mRNA were obtained for other cell lines (HEL and K562) with megakaryocytic properties, but not in HeLa cells. The increase in cyclin D1 was confirmed by Western immunoblotting of PMA-treated Dami cells. This finding suggested that cyclin D1 might participate in megakaryocyte differentiation by promoting endomitosis and/or inhibiting cell division. To address these possibilities, we constructed two stable Zn+2-inducible, cyclin D1-overexpressing Dami cell lines. Cyclin D1 expression alone was not sufficient to induce polyploidy, but in conjunction with PMA-induced differentiation, polyploidization was slightly enhanced. However, unlike other cell systems, cyclin D1 overexpression caused cessation of cell growth. Although the mechanism by which cyclin D1 may affect megakaryocyte differentiation is not clear, these data demonstrate that cyclin D1 is upregulated in differentiating megakaryocytic cells and may contribute to differentiation by arresting cell proliferation.

ANKHD1 Silencing Reduces In Vitro Clonogenicity and In Vivo Tumorogenicity Of Multiple Myeloma Cells

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3168-3168
Author(s):  
Anamika Dhyani ◽  
João Agostinho Machado-Neto ◽  
Patricia Favaro ◽  
Sara Teresinha Olalla Saad
Keyword(s):  
Cell Cycle ◽  
Gene Therapy ◽  
Multiple Myeloma ◽  
Cell Lines ◽  
Tumor Size ◽  
Control Group ◽  
Mice Model ◽  
And Migration

Abstract Introduction ANKHD1 is a multiple ankyrin repeats containing protein, highly expressed in cancers, such as acute leukemia. Earlier studies showed that ANKHD1 is highly expressed and plays important role in proliferation and cell cycle progression of multiple myeloma (MM) cells. It was also observed that ANKHD1 downregulation modulates cell cycle gene expression and upregulates p21 irresepective of TP53 mutational status of MM cell lines. Objective The present study aimed to study the effect ofANKHD1 silencing on MM growth both in vitro (clonogenicity, migration) and in vivo (xenograft tumor mice model). The purpose was to investigate the feasibility of ANKHD1 gene therapy for MM. Methods In the present study, ANKHD1 expression was silenced using short hairpin RNA (shRNA)-lentiviral delivery vector in MM cell lines (U266 and MM1S). For control MM cells were tranduced by lentiviral shRNA against LacZ. Downregulation of ANKHD1 expression was confirmed by qPCR and Western blot. Colony formation capacity and migration of control and ANKHD1 silenced MM cells was determined by methylcellulose and transwell migration assays, respectively. For in vivo MM growth, NOD-SCID mice were divided in two groups injected with control and ANKHD1 silenced cells, separately. Mice were observed daily for tumor growth. Once the tumor size reached 1 mm3, mice in both groups were sacrificed and tumor was excised to measure tumor volume and weight. Results Corroborating the results obtained in our earlier studies, in the present study also inhibition of ANKHD1 expression suppressed growth of MM cells in vitro. MM cell lines tranduced with ANKHD1 shRNA showed significantly low number of colonies ten days after plating in methylcellulose medium as compared to control (p<0.05). Similarly, in transwell migration assay, cell lines transduced with ANKHD1 showed significantly less migration as in response to 10% FBS at lower chamber as compared to control group (p<0.05) in both the cell lines analyzed. Further in xenograft MM mice model, the growth of tumor was visibly suppressed in mice injected with ANKHD1 silenced cells compared to control group. There was significant difference in tumor size (volume) between these 2 groups (P< 0.006). The tumor weight of the inhibition group was 0.71 ±0.2 g, significantly lighter than those of the control group (1.211 ± 0.5 g, P =0.02) Conclusion Our data indicates ANKHD1 downregulation significantly inhibits colony-forming ability and migration of both glucocorticoid resistant (U266) and sensitive (MM1S) MM cells. Further, gene silencing of ANKHD1 also resulted in reduced in vivo tumor growth in NOD/SCID mice. Collectively, the result obtained indicates that ANKHD1 may be a target for gene therapy in MM. Disclosures: No relevant conflicts of interest to declare.

Homeobox B9: A potential surrogate marker for bevacizumab in combination with chemotherapy in colorectal cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10531-10531
Author(s):  
Yoshinori Hoshino ◽  
Tetsu Hayashida ◽  
Akira Hirata ◽  
Koji Okabayashi ◽  
Hiroki Ochiai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Surrogate Marker ◽  
Angiogenic Factors ◽  
High Expression ◽  
Mrna Levels ◽  
Tgfβ Signaling ◽  
Bevacizumab Treatment

10531 Background: Homeobox B9 (HOXB9) is known to be overexpressed in human breast cancer and profoundly related to tumorigenicity, lung metastasis and radio-resistance. (Hayashida, PNAS 2010, and Chiba, PNAS 2011). However, little is known about the relation between the expression of HOXB9 and angiogenesis in colorectal cancer (CRC). We aimed to clarify the impact of HOXB9 in CRC and evaluate the importance for bevacizumab treatment. Methods: The expression of HOXB9 in human CRC specimens was analyzed. Then, we introduced HOXB9 construct into human CRC cell lines and examined TGFβ signaling and angiogenic factors. Xenograft model was established by these cell lines either with or without the administration of bevacizumab (5mg/kg, weekly) intraperitoneally. Finally, we examined the mRNA levels of consecutive patients who were treated by chemotherapy with bevacizumab in our institute and calculated the Kaplan- Meier curve with log-rank test. Results: 47 of 69 surgical specimens (67%) showed positive expression of HOXB9 mRNA. The high HOXB9 mRNA levels significantly correlated with poor differentiation and liver metastasis. The HOXB9-overexpressed cell lines showed significantly higher expression of TGFβ signaling target genes and angiogenic factors. HOXB9 overexpression significantly increased tumor volume and burden with higher microvessel density in vivo, even though the cell proliferation decreased in vitro. Notably, HOXB9-overexpressed tumor was dramatically shrunk by administration of bevacizumab (tumor shrinkage rate; 93% vs. 42% in HT29, 83% vs. 27% in HCT116). Patients with high expression of HOXB9 in tumor showed significantly longer progression free and overall survival periods (n=39). Conclusions: Our results demonstrated that patients with high expression of HOXB9 in tumor had better prognosis with bevacizumab treatment but worse without. In vivo and in vitro experiments revealed that HOXB9 might orchestrate angiogenesis and establish positive feedback between cancer cells and microenvironment. Bevacizumab might inhibit the feedback to reduce tumor growth dramatically. Therefore, HOXB9 may work as a potential surrogate marker of bevacizumab treatment in CRC.

The role of ZNF395 in renal cell carcinoma proliferation, migration, and invasion.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 592-592 ◽  
Author(s):  
Chen Zhao ◽  
Christopher G. Wood ◽  
Jose A. Karam ◽  
Tapati Maity ◽  
Lei Wang
Keyword(s):  
Renal Cell Carcinoma ◽  
Tumor Growth ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Renal Cell ◽  
Migration And Invasion ◽  
Mrna Levels

592 Background: Zinc finger protein 395 (ZNF395) is frequently altered in several tumor types. However, the role of ZNF395 remains poorly studied in patients with clear cell renal cell carcinoma (RCC). In this study, we investigated the in vitro and in vivo role of ZNF395 in ccRCC. Methods: cBioPortal For Cancer Genomics was used to correlate the expression of ZNF395 with RCC patient clinical, pathological and molecular profiles. ZNF395 protein and mRNA levels were studied in several RCC cell lines in vitro. Subsequently, ZNF395 knockdown was performed in 786-O and UMRC3 RCC cells and overexpression was done in Caki-1 and 769-P RCC cells. We then evaluated ZNF395 modulation in these cell lines by in vitro MTT, migration and invasion assays. Finally, we studied the effect of ZNF395 knockout and overexpression in vivo using SCID xenograft models. Results: Patients with higher expression of ZNF395 experienced longer disease-free survival and overall survival. Using in vitro models, we confirmed that knockdown of ZNF395 decreased ZNF395 expression, and increased proliferation, migration and invasiveness of 786-O and UMRC3, while overexpression of ZNF395 increased ZNF395 expression, and reduced proliferation, migration and invasiveness of Caki-1 and 769-P. Using in vivo mouse models, knockdown of ZNF395 expression in 786-O promoted tumor growth while its overexpression in Caki-1 resulted in tumor growth inhibition. We are currently performing experiments to understand the process by which ZNF395 regulates ccRCC pathogenesis. Conclusions: Our data support the role of ZNF395 as an important tumor suppressor gene in the pathogenesis of RCC.

Corilagin ameliorates schistosomiasis hepatic fibrosis through regulating IL-13 associated signal pathway in vitro and in vivo

Parasitology ◽  
2016 ◽  
Vol 143 (12) ◽  
pp. 1629-1638 ◽  
Author(s):  
HUA-RONG LI ◽  
GANG LI ◽  
MAN LI ◽  
SHU-LING ZHANG ◽  
HENG WANG ◽  
...  
Keyword(s):  
Hepatic Fibrosis ◽  
Quantitative Polymerase Chain Reaction ◽  
Signal Pathway ◽  
Signal Molecules ◽  
Mrna Levels ◽  
Protein Levels ◽  
Set Up ◽  
Inflammatory Changes

SUMMARYInterleukin (IL)-13-associated signal pathway plays an important role in schistosomiasis hepatic fibrosis. In this study we tried to investigate the effects of corilagin to ameliorate schistosomiasis hepatic fibrosis through regulating IL-13-associated signal pathway in vitro and in vivo. Cellular model was set up with hepatic stellate cells-T6 cells stimulated by rIL-13 and male Balb/c mice were infected with Schistosoma japonicum cercariaeas as animal model. Liver histological changes were observed with haematoxylin and eosin staining. Masson staining was employed to observe the change of egg granulomas. Expression of Col (collagen) and Col III were examined with Immunohistochemistry. Western bolt was employed to detect the JAK-1 and IL13Rα1 proteins. The mRNA expression of Col I, Col III, IL-13, JAK-1 and IL13Rα1 were tested by quantitative polymerase chain reaction. As a result, less inflammatory changes were found in all corilagin groups compared with model group and praziquantel group. The mRNA levels of Col I, Col III, IL-13, JAK-1 and IL13Rα1 were significantly decreased after corilagin intervention (P < 0·01). JAK-1 and IL-13Rα1 protein levels were also greatly decreased in the corilagin groups (P < 0·01). In conclusion, corilagin could ameliorate schistosomiasis hepatic fibrosis by down-regulating the expression of IL-13 and signal molecules in IL-13 pathway.

scholarly journals Quantitative Expression and Virus Transmission Analysis of DC-SIGN on Monocyte-Derived Dendritic Cells

2002 ◽  
Vol 76 (18) ◽  
pp. 9135-9142 ◽  
Author(s):  
Frédéric Baribaud ◽  
Stefan Pöhlmann ◽  
George Leslie ◽  
Frank Mortari ◽  
Robert W. Doms
Keyword(s):  
Dendritic Cells ◽  
Cell Lines ◽  
Ebola Virus ◽  
Virus Transmission ◽  
Virus Binding ◽  
Expression Levels ◽  
Quantitative Expression ◽  
Immunodeficiency Virus

ABSTRACT The C-type lectins DC-SIGN and DC-SIGNR efficiently bind human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) strains and can transmit bound virus to adjacent CD4-positive cells. DC-SIGN also binds efficiently to the Ebola virus glycoprotein, enhancing Ebola virus infection. DC-SIGN is thought to be responsible for the ability of dendritic cells (DCs) to capture HIV and transmit it to T cells, thus promoting HIV dissemination in vitro and perhaps in vivo as well. To investigate DC-SIGN function and expression levels on DCs, we characterized a panel of monoclonal antibodies (MAbs) directed against the carbohydrate recognition domain of DC-SIGN. Using quantitative fluorescence-activated cell sorter technology, we found that DC-SIGN is highly expressed on immature monocyte-derived DCs, with at least 100,000 copies and often in excess of 250,000 copies per DC. There was modest variation (three- to fourfold) in DC-SIGN expression levels between individuals and between DCs isolated from the same individual at different times. Several MAbs efficiently blocked virus binding to cell lines expressing human or rhesus DC-SIGN, preventing HIV and SIV transmission. Interactions with Ebola virus pseudotypes were also blocked efficiently. Despite their ability to block virus-DC-SIGN interactions on cell lines, these antibodies only inhibited transmission of virus from DCs by approximately 50% or less. These results indicate that factors other than DC-SIGN may play important roles in the ability of DCs to capture and transmit HIV.

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