Mesenchymal Stem Cell Differentiation Markers Shared with Soft Tissue Sarcomas

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4755-4755
Author(s):  
Stefan Wirths ◽  
Hans-Joerg Buehring ◽  
Lothar Kanz ◽  
Joerg T Hartmann ◽  
Hans-Georg Kopp
Keyword(s):  
Stem Cells ◽  
Soft Tissue ◽  
Expression Pattern ◽  
Cell Lines ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Soft Tissue Sarcomas ◽  
Stem Cell Differentiation ◽  
Antibody Panel

Abstract Malignant tumors are hypothesized to harbor small populations of self-renewing cancer stem cells. Targeting these cells may be the decisive step to overcome treatment resistance and achieve tumor eradication in cancer patients. Advanced soft tissue sarcomas (STS) are rare tumors with a dismal prognosis and a small number of systemic treatment options. STS may originate from mesenchymal stem cells (MSC); the latter have mainly been isolated from adult bone marrow (BM) as non-hematopoietic, self-renewing cells whose in vitro progeny comprises osteoblasts, chondroblasts, myocytes, and adipocytes. While in vitro expression profiles of MSC have been investigated extensively, the in vivo counterparts of MSC are still hypothetical. To target rare human cell BM populations including MSC, an exclusive antibody panel was developed. The target antigens include platelet-derived growth factor receptor-β (CD140b), HER-2/erbB2 (CD340), the recently described W8B2 antigen as well as several surface antigens identified by novel antibodies. To define the expression pattern of MSC-markers in STS, three STS cell lines were tested for expression of these antigens. In addition, snap-frozen primary STS sections were analyzed by immunohistochemistry using the same antibody panel. All cell lines revealed expression of selected markers including CD340, W8B2, and CD140b. Several MSC markers were restricted to a subpopulation of cells. In addition, leiomyosarcoma cells displayed a different expression pattern as compared to liposarcoma and Ewing’s sarcoma cells. Results of immunohistochemistry analysis of primary leiomyosarcoma tumor samples correlated strongly with expression patterns established by FACS analysis. However, important cytoarchitectural features regarding selected markers were revealed by immunohistochemistry: while primary leiomyosarcomas displayed uniform expression of W7C6, HEK3D6, CD10, and CD318, other markers such as CD34, W5C5, and 57D2 were expressed by tumor endothelia only. Moreover, a population of perivascular tumor cells was found to express the MSC-markers W4A5, W8B2, CD140b, W3D5, and W5C4. Novel MSC-markers are expressed by subpopulations in STS cell lines as well as in primary sarcoma tissue. Further studies on the functional significance of these phenotypical studies are underway and may help to identify novel specific targets recognizing the self-renewing STS-compartment.

scholarly journals Interspecies chimeric conditions affect the developmental rate of human pluripotent stem cells

2021 ◽  
Vol 17 (3) ◽  
pp. e1008778
Author(s):  
Jared Brown ◽  
Christopher Barry ◽  
Matthew T. Schmitz ◽  
Cara Argus ◽  
Jennifer M. Bolin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Cultures ◽  
Pluripotent Stem Cells ◽  
Time Course ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Human Pluripotent Stem Cells

Human pluripotent stem cells hold significant promise for regenerative medicine. However, long differentiation protocols and immature characteristics of stem cell-derived cell types remain challenges to the development of many therapeutic applications. In contrast to the slow differentiation of human stem cells in vitro that mirrors a nine-month gestation period, mouse stem cells develop according to a much faster three-week gestation timeline. Here, we tested if co-differentiation with mouse pluripotent stem cells could accelerate the differentiation speed of human embryonic stem cells. Following a six-week RNA-sequencing time course of neural differentiation, we identified 929 human genes that were upregulated earlier and 535 genes that exhibited earlier peaked expression profiles in chimeric cell cultures than in human cell cultures alone. Genes with accelerated upregulation were significantly enriched in Gene Ontology terms associated with neurogenesis, neuron differentiation and maturation, and synapse signaling. Moreover, chimeric mixed samples correlated with in utero human embryonic samples earlier than human cells alone, and acceleration was dose-dependent on human-mouse co-culture ratios. The altered gene expression patterns and developmental rates described in this report have implications for accelerating human stem cell differentiation and the use of interspecies chimeric embryos in developing human organs for transplantation.

Cellular and gene expression patterns associated with root bifurcation in Selaginella

2022 ◽  
Author(s):  
Tom Beeckman ◽  
Tao Fang ◽  
Hans Motte ◽  
Boris Parizot ◽  
Wouter Smet ◽  
...  
Keyword(s):  
Stem Cells ◽  
Root Meristem ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Root Apex ◽  
Time Frame ◽  
Developmental Time ◽  
Transcriptional Level ◽  
Root Branching

The roots of lycophytes branch through dichotomy or bifurcation, which means that the root apex splits into two daughter roots. This is morphologically distinct from lateral root (LR) branching in the extant euphyllophytes, where LRs develop along the root axis at different distances from the apex. The process of root bifurcation is poorly understood, while such knowledge can be important, as it may represent an evolutionarily ancient strategy that roots recruited to form new stem cells or meristems. In this study, we examined root bifurcation in the lycophyte Selaginella moellendorffii. We characterized an in vitro developmental time-frame based on repetitive apex bifurcations, allowing us to sample different stages of dichotomous root branching and analyze the root meristem and root branching in S. moellendorffii at the microscopical and transcriptional level. Our results show that, in contrast to previous assumptions, initial cells in the root meristem are mostly not tetrahedral but rather show an irregular shape. Tracking down the early stages during root branching argues for the occurrence of a symmetric division of the single initial cell resulting in two apical stem cells allowing for root meristem bifurcation. Moreover, we generated a S. moellendorffii root branching transcriptome, which resulted in the delineation of a subset of core meristem genes. The occurrence of multiple meristem-related orthologues in this dataset, including inversely correlated expression profiles of a SCARECROW (SCR) versus a RETINOBLASTOMA-RELATED1 (RBR1) homologue suggests the presence of conserved pathways in the control of meristem and root stem cell establishment or maintenance.

Detection of MSC-like cells in soft tissue sarcoma cell lines and primary tumors

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11000-11000
Author(s):  
S. Wirths ◽  
E. Malenke ◽  
T. Wiesner ◽  
H. Buehring ◽  
J. Hartmann ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Cell Lines ◽  
Primary Tumor ◽  
Growth Factor Receptor ◽  
Soft Tissue Sarcomas ◽  
Proliferative Capacity ◽  
Differentiation Potential ◽  
Primary Tumors

11000 Background: Soft tissue sarcomas (STS) are a heterogeneous group of mesodermal tumors hypothetically originating from mesenchymal stem cells (MSC). While the expression profile of bone marrow derived MSCs and their in vitro differentiation potential have been examined extensively, knowledge regarding the in vivo counterparts of MSC is still evolving. We hypothesized that MSC-like cells within STS could represent sarcoma initiating cells. Methods: To target rare human cell populations including MSCs, an exclusive antibody panel was developed. The target antigens include platelet-derived growth factor receptor-β (CD140b), HER-2/erbB2 (CD340), TNFRSF16 (CD217), frizzled-4 (CD344), the recently described W8B2 antigen, as well as several surface antigens identified by novel antibodies. To define the expression pattern of MSC-markers in STS, both cell lines and primary tumor samples in suspension and in snap frozen sections were investigated. To reveal functional differences between identified rare tumor populations single cell proliferation kinetics were investigated after FACS-sorting. Results: All cell lines und primary tumor samples revealed expression of selected markers. Antigens identifying subpopulations within all sarcoma samples investigated, were selected for functional studies. These included frizzled-4, TNFRSF16, W5C5 and W8B2. Liposarcoma (SW872), leiomyosarcoma (SK-LMS) and fibrosarcoma (HT1080) cell lines enclosed subpopulations with differential expression of above markers and by FACS based limiting dilution it was demonstrated that only fractions of viable cells contained proliferative capacity. Cells lacking expression of CD271 had lower proliferative capacity compared to mock sorted HT1080 or SK-LMS, while CD271+ SW872 had significantly higher proliferation. The antigen defined by W5C5 identified cells with high proliferative capacity compared to control in SW872 and SK-LMS and its lack in HT1080 identified a subpopulation with largely reduced proliferation. Conclusions: Subpopulations within STS cell lines and primary sarcoma tissue express novel MSC-markers and display increased proliferative capacity, potentially reflecting the existence of sarcoma initiating cells. No significant financial relationships to disclose.

scholarly journals Identification and Characterization of Long Non-Coding RNAs in Osteogenic Differentiation of Human Adipose-Derived Stem Cells

2017 ◽  
Vol 42 (3) ◽  
pp. 1037-1050 ◽  
Author(s):  
Guangxin Huang ◽  
Yan Kang ◽  
Zhiyu Huang ◽  
Zhiqi Zhang ◽  
Fangang Meng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Osteogenic Differentiation ◽  
Expression Profile ◽  
Expression Profiles ◽  
Stem Cell Differentiation ◽  
Adipose Derived Stem Cells ◽  
Bioinformatics Analyses ◽  
Human Ascs ◽  
Global Expression Profile

Background/Aims: Long noncoding RNAs (lncRNAs) play important roles in stem cell differentiation. However, their role in osteogenesis of human adipose-derived stem cells (ASCs), a promising cell source for bone regeneration, remains unknown. Here, we investigated the expression profile and potential roles of lncRNAs in osteogenic differentiation of human ASCs. Methods: Human ASCs were induced to differentiate into osteoblasts in vitro, and the expression profiles of lncRNAs and mRNAs in undifferentiated and osteogenic differentiated ASCs were obtained by microarray. Bioinformatics analyses including subgroup analysis, gene ontology analysis, pathway analysis and co-expression network analysis were performed. The function of lncRNA H19 was determined by in vitro knockdown and overexpression. Quantitative reverse transcription polymerase chain reaction was utilized to examine the expression of selected genes. Results: We identified 1,460 upregulated and 1,112 downregulated lncRNAs in osteogenic differentiated human ASCs as compared with those of undifferentiated cells (Fold change ≥ 2.0, P < 0.05). Among these, 94 antisense lncRNAs, 85 enhancer-like lncRNAs and 160 lincRNAs were further recognized. We used 12 lncRNAs and 157 mRNAs to comprise a coding-non-coding gene expression network. Additionally, silencing of H19 caused a significantly increase in expression of osteogenesis-related genes, including ALPL and RUNX2, while a decrease was observed after H19 overexpression. Conclusion: This study revealed for the first time the global expression profile of lncRNAs involved in osteogenic differentiation of human ASCs and provided a foundation for future investigations of lncRNA regulation of human ASC osteogenesis.

scholarly journals Detection of Novel Potential Regulators of Stem Cell Differentiation and Cardiogenesis through Combined Genome-Wide Profiling of Protein-Coding Transcripts and microRNAs

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2477
Author(s):  
Rui Machado ◽  
Agapios Sachinidis ◽  
Matthias E. Futschik
Keyword(s):  
Stem Cells ◽  
Gene Regulation ◽  
Heart Development ◽  
Expression Patterns ◽  
Mirna Gene ◽  
Stem Cell Differentiation ◽  
In Vitro Differentiation ◽  
Genome Wide

In vitro differentiation of embryonic stem cells (ESCs) provides a convenient basis for the study of microRNA-based gene regulation that is relevant for early cardiogenic processes. However, to which degree insights gained from in vitro differentiation models can be readily transferred to the in vivo system remains unclear. In this study, we profiled simultaneous genome-wide measurements of mRNAs and microRNAs (miRNAs) of differentiating murine ESCs (mESCs) and integrated putative miRNA-gene interactions to assess miRNA-driven gene regulation. To identify interactions conserved between in vivo and in vitro, we combined our analysis with a recent transcriptomic study of early murine heart development in vivo. We detected over 200 putative miRNA–mRNA interactions with conserved expression patterns that were indicative of gene regulation across the in vitro and in vivo studies. A substantial proportion of candidate interactions have been already linked to cardiogenesis, supporting the validity of our approach. Notably, we also detected miRNAs with expression patterns that closely resembled those of key developmental transcription factors. The approach taken in this study enabled the identification of miRNA interactions in in vitro models with potential relevance for early cardiogenic development. Such comparative approaches will be important for the faithful application of stem cells in cardiovascular research.

scholarly journals IL-1-conferred gene expression pattern in ERα+ BCa and AR+ PCa cells is intrinsic to ERα- BCa and AR- PCa cells and promotes cell survival

2019 ◽  
Author(s):  
Afshan F. Nawas ◽  
Mohammed Kanchwala ◽  
Shayna E. Thomas-Jardin ◽  
Haley Dahl ◽  
Kelly Daescu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Pattern ◽  
Cell Lines ◽  
Interleukin 1 ◽  
Expression Patterns ◽  
Gene Expression Pattern ◽  
Treatment Resistance ◽  
Rna Seq ◽  
Drug Inhibition

Abstract Background: Breast (BCa) and prostate (PCa) cancers are hormone receptor (HR)-driven cancers. Thus, BCa and PCa patients are given therapies that reduce hormone levels or directly blocks HR activity; but most patients eventually develop treatment resistance. We have previously reported that interleukin-1 (IL-1) inflammatory cytokine downregulates ER𝛼 and AR mRNA in HR-positive (HR+) BCa and PCa cell lines, yet the cells can remain viable. Additionally, we identified pro-survival proteins and processes upregulated by IL-1 in HR+ BCa and PCa cells, that are basally high in HR- BCa and PCa cells. Therefore, we hypothesize that IL-1 confers a conserved gene expression pattern in HR+ BCa and PCa cells that mimics conserved basal gene expression patterns in HR- BCa and PCa cells to promote HR-independent survival and tumorigenicity.Methods: We performed RNA sequencing (RNA-seq) for HR+ BCa and PCa cell lines exposed to IL-1 and for untreated HR- BCa and PCa cell lines. We confirmed expression patterns of select genes by RT-qPCR and used siRNA and/or drug inhibition to silence select genes in HR- BCa cell lines. Finally, we performed Ingenuity Pathway Analysis (IPA) to identify signaling pathways encoded by our RNA-seq data set.Results: We identified 350 genes in common between BCa and PCa cells that are induced or repressed by IL-1 in HR+ cells that are, respectively, basally high or low in HR- cells. Among these genes, we identified Sequestome-1 (SQSTM1/p62) and SRY (Sex-Determining Region Y)-Box 9 (SOX9) to be essential for survival of HR- BCa and PCa cell lines. Analysis of publicly available data indicates that p62 and SOX9 expression are elevated in HR-independent BCa and PCa sublines generated in vitro, suggesting that p62 and SOX9 have a role in acquired treatment resistance. We also assessed HR- cell line viability in response to the p62-targeting drug, verteporfin, and found that verteporfin is cytotoxic for HR- cell lines. Conclusions: Our 350 gene set can be used to identify novel therapeutic targets and/or biomarkers conserved among acquired (e.g. due to inflammation) or intrinsic HR-independent BCa and PCa.

scholarly journals IL-1-conferred gene expression pattern in ERα+ BCa and AR+ PCa cells is intrinsic to ERα− BCa and AR− PCa cells and promotes cell survival

2019 ◽  
Author(s):  
Afshan F. Nawas ◽  
Mohammed Kanchwala ◽  
Shayna E. Thomas-Jardin ◽  
Haley Dahl ◽  
Kelly Daescu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Pattern ◽  
Cell Lines ◽  
Interleukin 1 ◽  
Expression Patterns ◽  
Gene Expression Pattern ◽  
Treatment Resistance ◽  
Rna Seq ◽  
Data Set

ABSTRACTBackgroundBreast (BCa) and prostate (PCa) cancers are hormone receptor (HR)-driven cancers. Thus, BCa and PCa patients are given therapies that reduce hormone levels or directly blocks HR activity; but most patients eventually develop treatment resistance. We have previously reported that interleukin-1 (IL-1) inflammatory cytokine downregulates ERα and AR mRNA in HR-positive (HR+) BCa and PCa cell lines, yet the cells can remain viable. Additionally, we identified pro-survival proteins and processes upregulated by IL-1 in HR+ BCa and PCa cells, that are basally high in HR− BCa and PCa cells. Therefore, we hypothesize that IL-1 confers a conserved gene expression pattern in HR+ BCa and PCa cells that mimics conserved basal gene expression patterns in HR− BCa and PCa cells to promote HR-independent survival and tumorigenicity.MethodsWe performed RNA sequencing (RNA-seq) for HR+ BCa and PCa cell lines exposed to IL-1 and for untreated HR− BCa and PCa cell lines. We confirmed expression patterns of select genes by RT-qPCR and used siRNA and/or drug inhibition to silence select genes in HR− BCa cell lines. Finally, we performed Ingenuity Pathway Analysis (IPA) to identify signaling pathways encoded by our RNA-seq data set.ResultsWe identified 350 genes in common between BCa and PCa cells that are induced or repressed by IL-1 in HR+ cells that are, respectively, basally high or low in HR− cells. Among these genes, we identified Sequestome-1 (SQSTM1/p62) and SRY (Sex-Determining Region Y)-Box 9 (SOX9) to be essential for survival of HR− BCa and PCa cell lines. Analysis of publicly available data indicates that p62 and SOX9 expression are elevated in HR-independent BCa and PCa sublines generated in vitro, suggesting that p62 and SOX9 have a role in acquired treatment resistance. We also assessed HR− cell line viability in response to the p62-targeting drug, verteporfin, and found that verteporfin is cytotoxic for HR− cell lines.ConclusionsOur 350 gene set can be used to identify novel therapeutic targets and/or biomarkers conserved among acquired (e.g. due to inflammation) or intrinsic HR-independent BCa and PCa.

scholarly journals IL-1-conferred gene expression pattern in ERα+ BCa and AR+ PCa cells is intrinsic to ERα- BCa and AR- PCa cells and promotes cell survival

2019 ◽  
Author(s):  
Afshan F. Nawas ◽  
Mohammed Kanchwala ◽  
Shayna E. Thomas-Jardin ◽  
Haley Dahl ◽  
Kelly Daescu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Pattern ◽  
Cell Lines ◽  
Hormone Receptor ◽  
Interleukin 1 ◽  
Expression Patterns ◽  
Gene Expression Pattern ◽  
Treatment Resistance ◽  
Rna Seq

Abstract Background Breast (BCa) and prostate (PCa) cancers are hormone receptor (HR)-driven cancers. Thus, BCa and PCa patients are given therapies that reduce hormone levels or directly blocks HR activity; but most patients eventually develop treatment resistance. We have previously reported that interleukin-1 (IL-1) inflammatory cytokine downregulates ERα and AR mRNA in HR-positive (HR+) BCa and PCa cell lines, yet the cells can remain viable. Additionally, we identified pro-survival proteins and processes upregulated by IL-1 in HR+ BCa and PCa cells, that are basally high in HR- BCa and PCa cells. Therefore, we hypothesize that IL-1 confers a conserved gene expression pattern in HR+ BCa and PCa cells that mimics conserved basal gene expression patterns in HR- BCa and PCa cells to promote HR-independent survival and tumorigenicity.Methods We performed RNA sequencing (RNA-seq) for HR+ BCa and PCa cell lines exposed to IL-1 and for untreated HR- BCa and PCa cell lines. We confirmed expression patterns of select genes by RT-qPCR and used siRNA and/or drug inhibition to silence select genes in HR- BCa cell lines. Finally, we performed Ingenuity Pathway Analysis (IPA) and used the gene ontology web-based tool, GOrilla, to identify signaling pathways encoded by our RNA-seq data set.Results We identified 350 genes in common between BCa and PCa cells that are induced or repressed by IL-1 in HR+ cells that are, respectively, basally high or low in HR- cells. Among these genes, we identified Sequestome-1 (SQSTM1/p62) and SRY (Sex-Determining Region Y)-Box 9 (SOX9 ) to be essential for survival of HR- BCa and PCa cell lines. Analysis of publicly available data indicates that p62 and SOX9 expression are elevated in HR-independent BCa and PCa sublines generated in vitro, suggesting that p62 and SOX9 have a role in acquired hormone receptor independence and treatment resistance. We also assessed HR- cell line viability in response to the p62-targeting drug, verteporfin, and found that verteporfin is cytotoxic for HR- cell lines. Conclusions Our 350 gene set can be used to identify novel therapeutic targets and/or biomarkers conserved among acquired (e.g. due to inflammation) or intrinsic HR-independent BCa and PCa.

165 Effect of Dimethyl Sulfoxide Supplementation During In Vitro Maturation on the Genetic Expression Pattern of Bovine Blastocyst

2018 ◽  
Vol 30 (1) ◽  
pp. 222
Author(s):  
A. E. Ynsaurralde-Rivolta ◽  
M. Suvá ◽  
R. Bevacqua ◽  
L. Rodriguez-Alvarez ◽  
A. Velasquez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Fragmentation ◽  
Expression Pattern ◽  
In Vitro Maturation ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Stem Cell Differentiation ◽  
Marker Genes ◽  
Vitro Fertilization

Supplementation of bovine oocytes with 0.5% (v/v) dimethylsulfoxide (DMSO) during in vitro maturation (IVM) results in increased blastocysts rates (Ynsaurralde et al. 2016 Reprod. Fertil. Dev. 29, 201-202). Recently, an important role of DMSO in stem cell differentiation has been observed, attributed to modulation of gene expression. However, the effect of DMSO suplementation during in vitro maturation on gene expression profiles and embryo quality have not been evaluated so far. Thus, we examinated the effect of DMSO during IVM on the expression of some key genes (Sox2, Oct4, and Cdx2) and on the degree of DNA fragmentation at the blastocyst stage. To this aim, cumulus–oocyte complexes collected from slaughterhouse ovaries were matured in TCM-199 containing 10% fetal bovine serum, 10 µg mL−1 FSH, 0.3 mM sodium pyruvate, 100 mM cysteamine, and 2% antibiotic-antimycotic for 24 h, at 6.5% CO2 in humidified air and 38.5°C. Maturation media was supplemented with 0, 0.5, or 0.75% (v/v) DMSO. In vitro fertilization (IVF) was performed with 16 × 106 spermatozoa per mL for 5 h. Afterwards, presumptive zygotes were cultured in SOF for 7 days at 38.5°C and 5% O2. Three pools of 5 blastocysts were analysed for each treatment. Gene expression analysis was performed by real-time qPCR and DNA fragmentation of blastocysts was measured by TUNEL assay (n = 8, 7, and 14 blastocysts analysed for 0, 0.5, and 0.75% v/v DMSO, respectively). The results were statistically analysed using ANOVA with a completely randomised model by InfoStat software Version 1.1 (https://www.infostat.com.ar/). The pluripotency marker genes Sox2 and Oct4 were up-regulated in blastocysts only when the oocytes were matured in 0.75% DMSO, whereas the trophoblastic marker Cdx2 showed no differences among treatments. No differences were detected in the number of TUNEL-positive cells among treatments: 10/65 (15%) in 0%, 19/110 (18%) in 0.5%, and 18/98 (20%) in 0.75% (v/v) DMSO. In conclusion, supplementation with 0.5% (v/v) DMSO, as previously published, increases the production of blastocysts without disrupting the expression pattern of the evaluated genes.

scholarly journals Modeling the Diversity of Epithelial Ovarian Cancer through Ten Novel Well Characterized Cell Lines Covering Multiple Subtypes of the Disease

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2222 ◽  
Author(s):  
Alexandre Sauriol ◽  
Kayla Simeone ◽  
Lise Portelance ◽  
Liliane Meunier ◽  
Kim Leclerc-Desaulniers ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Complex Disease ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Cancer Cell Lines ◽  
Future Research

Cancer cell lines are amongst the most important pre-clinical models. In the context of epithelial ovarian cancer, a highly heterogeneous disease with diverse subtypes, it is paramount to study a wide panel of models in order to draw a representative picture of the disease. As this lethal gynaecological malignancy has seen little improvement in overall survival in the last decade, it is all the more pressing to support future research with robust and diverse study models. Here, we describe ten novel spontaneously immortalized patient-derived ovarian cancer cell lines, detailing their respective mutational profiles and gene/biomarker expression patterns, as well as their in vitro and in vivo growth characteristics. Eight of the cell lines were classified as high-grade serous, while two were determined to be of the rarer mucinous and clear cell subtypes, respectively. Each of the ten cell lines presents a panel of characteristics reflective of diverse clinically relevant phenomena, including chemotherapeutic resistance, metastatic potential, and subtype-associated mutations and gene/protein expression profiles. Importantly, four cell lines formed subcutaneous tumors in mice, a key characteristic for pre-clinical drug testing. Our work thus contributes significantly to the available models for the study of ovarian cancer, supplying additional tools to better understand this complex disease.

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