Expression profile of PC-3-derived cell lines from transendothelial migration or in vivo metastasis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE56410 | GEO | 2014/04/10
SECONDARY ACCESSION(S): PRJNA243266
REPOSITORIES: GEO
Similar Datasets
Project description:Metastatic colonization involves cancer cell lodgment or adherence in the microvasculature and subsequent migration of those cells across the endothelium into a secondary organ site. To study this process further, we analyzed both in vitro and in vivo migration of human PC-3 prostate cancer cells . We isolated 6 subpopulation of cells: TEM4-18 were isolated from in vitro transendothelial migration of PC-3 cells; GS672.Ug, GS683.LALN and JD1203.Lu are single passaged in vivo cell lines from TEM4-18; GS689.Li and GS694.LAd are twice passaged in vivo cell lines from PC-3 cells. All the subpopulations crossed an endothelial barrier more efficiently and more aggressive in a murine metastatic colonization model than parental PC-3 cells. Microarray and FACS analysis of these cells showed that the expression of many genes previously associated with leukocyte trafficking and cancer cell extravasation were either unchanged or down-regulated. These cells exhibited characteristic molecular markers of an epithelial-to-mesenchymal transition, including frank loss of E-cadherin expression and upregulation of the E-cadherin repressor ZEB1. We used microarray to detail the global programme of gene expression underlying cancer metastasis. We wanted to compare the expression profiles of cells that had undergone transendothelial migration in vitro or metastasis in vivo. TEM4-18 was generated from the parental PC-3 that was plated onto a confluent human microvascular endothelial cell line from the lung and allowed to migrate across this monolayer. GS672.Ug were isolated from urogenital after intravenous injection of PC-3 cells. GS683.LALN and JD1203.Lu were isolated from lung after intravenous injection of TEM-418 cells. JD549.Ki were isolated from kidney after intravenous injection PC-3 cells. GS689.Li and GS694.LAd were isolated from liver and left adrenal after intravenous injection of JD549.Ki. All the cell lines are analyzed once except duplicate for TEM4-18 in this experiment for a total of 7 samples in this microarray. All other five sublines were then compared to TEM4-18 cells for changes in gene expression.
2014-04-10 | E-GEOD-56410 | biostudies-arrayexpress
Project description:Metastatic colonization involves cancer cell lodgment or adherence in the microvasculature and subsequent migration of those cells across the endothelium into a secondary organ site. To study this process further, we analyzed transendothelial migration of human PC-3 prostate cancer cells in vitro. We isolated a subpopulation of cells, TEM4-18, that crossed an endothelial barrier more efficiently, but surprisingly, were less invasive than parental PC-3 cells in other contexts in vitro. Importantly, TEM4-18 cells were more aggressive than PC-3 cells in a murine metastatic colonization model. Microarray and FACS analysis of these cells showed that the expression of many genes previously associated with leukocyte trafficking and cancer cell extravasation were either unchanged or down-regulated. TEM4-18 cells exhibited characteristic molecular markers of an epithelial-to-mesenchymal transition (EMT), including frank loss of E-cadherin expression and upregulation of the E-cadherin repressor ZEB1. Silencing ZEB1 in TEM4-18 cells resulted in increased E-cadherin and reduced transendothelial migration. TEM4-18 cells also express N-cadherin, which was found to be necessary, but not sufficient for increased transendothelial migration. Our results extend the role of EMT in metastasis to transendothelial migration and implicate ZEB1 and N-cadherin in this process in prostate cancer cells.
2009-01-15 | GSE14405 | GEO
Project description:Metastatic colonization involves cancer cell lodgment or adherence in the microvasculature and subsequent migration of those cells across the endothelium into a secondary organ site. To study this process further, we analyzed transendothelial migration of human PC-3 prostate cancer cells in vitro. We isolated a subpopulation of cells, TEM4-18, that crossed an endothelial barrier more efficiently, but surprisingly, were less invasive than parental PC-3 cells in other contexts in vitro. Importantly, TEM4-18 cells were more aggressive than PC-3 cells in a murine metastatic colonization model. Microarray and FACS analysis of these cells showed that the expression of many genes previously associated with leukocyte trafficking and cancer cell extravasation were either unchanged or down-regulated. TEM4-18 cells exhibited characteristic molecular markers of an epithelial-to-mesenchymal transition (EMT), including frank loss of E-cadherin expression and upregulation of the E-cadherin repressor ZEB1. Silencing ZEB1 in TEM4-18 cells resulted in increased E-cadherin and reduced transendothelial migration. TEM4-18 cells also express N-cadherin, which was found to be necessary, but not sufficient for increased transendothelial migration. Our results extend the role of EMT in metastasis to transendothelial migration and implicate ZEB1 and N-cadherin in this process in prostate cancer cells. Experiment Overall Design: We wanted to compare the expression profiles of cells that had undergone transendothelial migration. The parental, and reference cell line, PC-3 was plated onto a confluent human microvascular endothelial cell line from the lung and allowed to migrate across this monolayer. A new cell line, TEM4-18, was isolated from this experiment. We also performed this experiment a second time to isolate a biological replicate of the TEM4-18 cell line, termed TEM2-5. All 3 cell lines, PC-3, TEM4-18, and TEM2-5 are analyzed as replicates in this experiment for a total of 6 samples in this microarray. Both TEM4-18 and TEM2-5 were then compared to PC-3 cells for changes in gene expression.
2009-01-25 | E-GEOD-14405 | biostudies-arrayexpress
Project description:Metastasis is a major obstacle to better prognosis in patients with hepatocellular carcinoma (HCC). Mesenchymal-epithelial transition (MET) is the driving force for metastatic colonization in which E-cadherin reexpression is a critical procedure. It has been reported that the loss of paired-related homeobox transcription factor 1 (PRRX1) is required for cancer cell metastasis in vivo. However, the role of PRRX1 in MET and how its downregulation triggers E-cadherin reexpression are unknown. In this study, we performed a systematic, mechanistic study regarding the role of PRRX1 in MET of HCC. We observed PRRX1 downregulation in HCC tissues which correlated with early metastasis and short overall survival time. Overexpression of PRRX1 induced EMT, but did not promote metastasis formation, while knockdown of PRRX1 promoted metastasis and colonization of circulating HCC cells as shown in in situ liver tumor model and colonization model. PRRX1 protein levels reversely correlated with E-cadherin levels in HCC cell lines. PRRX1 knockdown promoted E-cadherin reexpression and cell proliferation, inhibited cell invasion and migration. The microarray results showed that PRRX1 deficiency regulated extracellular matrix (ECM) interaction, focal adhesion, TGF-β signaling and cancer pathways. PRRX1 knockdown upregulated PITX2 (paired like homeodomain 2) and inhibited CTNNB1 (catenin beta 1) and SLUG. Silencing of PITX2 reversed CTNNB1 and SLUG inhibition and E-cadherin reexpression. PITX2 upregulation increased miR-200a and miR-200b/429, which further inhibited the transcription of CTNNB1 and SLUG, respectively, thus abrogating the inhibitory effect on E-cadherin. In conclusion, our data showed that the downregulation of PRRX1 induced E-cadherin reexpression through PITX2/miR-200a/CTNNB1 and PITX2/miR-200b/429/SLUG pathway, making PRRX1 a novel prognostic factor for HCC.
2020-04-18 | GSE148851 | GEO
Project description:Breast cancer metastasis is driven by profound remodeling of the intracellular cytoskeleton enabling efficient cell migration. Anillin is a unique cytoskeletal scaffolding protein that regulates actin filaments, microtubules, septin polymers and Rho GTPases. Anillin is markedly overexpressed in breast cancer and other solid cancer, however its functions in cancer cells remain poorly understood. This study aims at investigating the roles of anillin in regulating breast cancer cell migration, invasion and metastasis. CRISPR/Cas9 technology was used to deplete anillin in highly metastatic MDA-MB-231and BT549 cells and to overexpress it in poorly invasive MCF10AneoT cells. These loss-of-function and gain-of-function studies demonstrated that anillin is necessary and sufficient to accelerate migration, invasion and anchorage-independent growth of breast cancer cells in vitro. Furthermore, loss of anillin markedly attenuated both primary tumor growth and metastasis of breast cancer in vivo. In breast cancer cells, anillin was localized in the nucleus, however anillin knockout affected the cytoplasmic/cortical events such as the organization of actin cytoskeleton and cell-matrix adhesions. This was accompanied by a global transcriptional reprogramming of anillin-depleted breast cancer cells that resulted in suppression of their stemness and induction of the mesenchymal to epithelial trans-differentiation. Such trans-differentiation was manifested by upregulation of basal keratins along with increased expression of E-cadherin and P-cadherin. Knockdown of E-cadherin reversed attenuated migration and invasion of anillin-deficient cells. Our study provides the first evidence that anillin plays causal roles in breast cancer development and metastasis in vitro and in vivo and unravels novel functions of anillin in regulating breast cancer stemness and differentiation.
2020-01-01 | GSE131120 | GEO
Project description:Dysfunction in long noncoding RNAs (lncRNAs) is reported to participate in the initiation and progression of human cancer; however, the biological functions and molecular mechanisms through which lncRNAs affect pancreatic cancer (PC) are largely unknown. Here, we report a novel lncRNA, LINC01111, that is clearly downregulated in PC tissues and plasma of PC patients and acts as a tumor suppressor. We found that the LINC01111 level was negatively correlated with the TNM stage but positively correlated with the survival of PC patients. The overexpression of LINC01111 significantly inhibited cell proliferation, the cell cycle, and cell invasion and migration in vitro, as well as tumorigenesis and metastasis in vivo. Conversely, the knockdown of LINC01111 enhanced cell proliferation, the cell cycle, and cell invasion and migration in vitro, as well as tumorigenesis and metastasis in vivo. Furthermore, we found that high expression levels of LINC01111 upregulated DUSP1 levels by sequestering miR-3924, resulting in the blockage of SAPK phosphorylation and the inactivation of the SAPK/JNK signaling pathway in PC cells and thus inhibiting PC aggressiveness. Overall, these data reveal that LINC01111 is a potential diagnostic biomarker for PC patients, and the newly identified LINC01111/miR-3924/DUSP1 axis can modulate PC initiation and development.
2019-10-05 | GSE138420 | GEO
Project description:MTI-101 is a first-in-class novel cyclic peptide shown to have anti-tumor activity in both multiple myeloma and castrate-resistant prostate in vivo cancer models. These data suggest the potential for a broad spectrum of anti-cancer activity for this class of compounds. To further delineate determinants of sensitivity and resistance that were not dependent on oncogenic drivers, two isogenic drug resistant cell lines were generated with chronic exposure to MTI-101 in a non-small cell lung cancer (NSCLC) PC-9 (EGFR driven) and a small cell lung cancer (SCLC) H446 (PTEN deleted and c-MYC amplified). Using the isogenic cell line systems coupled with RNA-SEQ, the top enriched GSEA hallmark was downregulation of genes that contribute to epithelial to mesenchymal transition (EMT), a finding that was consistent in both acquired MTI-101 selected resistant cell lines. The RNA-SEQ data correlated with predicted changes in the phenotype, including significant decreased invasion in Matrigel and changes of EMT markers (E-Cadherin, Vimentin and Twist) at the protein level. Furthermore, in the EGFR driven PC-9 cell line, selection for resistance towards MTI-101 resulted in collateral sensitivity toward EGFR inhibitors. To determine the stability of the MET phenotype, cells were removed from drug and tested for invasion and drug resistance every month. These data indicated that the mesenchymal to epithelial transition (MET) phenotype and genotype was stable for a minimum of six months. MTI-101 treatment in PC-9 and H446 cells showed synergistic activity with the standard of care agents Erlotinib, Osimertinib, and Cisplatin when used in combination in PC-9 and H446 cells, respectively. Finally, in vivo data indicates that MTI-101 treatment selects for increased E-Cadherin and decreased Vimentin in H446. In addition, treatment with MTI-101 decreased incidence of bone metastasis in the PC-9 in vivo model. Together, these data indicate that MTI-101 treatment could be used as a tool to delay the emergence of metastatic disease for the treatment of lung cancer.
2022-07-13 | GSE193455 | GEO
Project description:Cadherin-11 expression is associated with tumor progression and metastasis in various cancers, including basal-like breast carcinoma and advanced prostate cancer, and invasive cell lines, yet is absent in normal epithelium. We now show cadherin-11 attenuation in aggressive breast and prostate cancer cells results in marked decreases in proliferation, migration, and invasion. Cadherin-11 depletion in MDA-231 cells prevents tumor growth in mice and alters gene expression associated with poor prognosis malignancies. Additionally, a novel small molecule inhibitor targeting its unique adhesive interface significantly inhibits the growth and migration of cadherin-11 positive cells. Cadherin-11 is essential for malignant progression of MDA-231 basal-type cells, and may serve as both an aggressive tumor marker and viable therapeutic target for poor prognosis carcinomas expressing it.
2010-02-22 | GSE14943 | GEO
Project description:The aberrant activation of HER2 has a pivotal role in bone metastasis implantation and progression in several tumor types, in-cluding prostate cancer (PC). Trastuzumab and other anti-HER2 therapies, such as lapatinib, have been used in human breast cancer HER2 positive. Although HER2 overexpression has been reported in PC, anti-HER2 therapy response has revealed conflicting results. We investigated the potential of lapatinib in inhibiting cell migration and inducing apoptosis in two human (LNCaP and PC3) and two canine PC cell lines (PC1 and PC2). Cell migration and apoptosis were evaluated by Annexin V/PI analysis after lapatinib treatment. The transcriptome analysis of all cell lines before and after treatment with lapatinib was also performed. We found increased apoptosis and migration inhibition in LNCaP cells (androgen-sensitive cell line), while PC1, PC2, and PC3 cells showed no alterations after the treatment. The transcriptome analysis of LNCaP and PC3 cell lines showed 158 dysregulated transcripts in common, while PC1 and PC2 cell lines presented 82. At the doses of lapatinib used, we observed transcriptional modifications in all cell lines. PI3K/AKT/mTOR pathway were enriched in human PC cells, while canine PC cells showed en-richment of tyrosine kinase antitumor response and HER2-related pathways. In canine PC cells, the apoptosis failed after lapatinib treatment, possibly due to the downregulation of MAPK genes. Prostate cancer cells insensitive to androgens may be resistant to lapatinib through PI3K gene dysregulation. The association of lapatinib with PI3K inhibitors may provide a more effective anti-tumor response and clinical benefits to PC patients.
2023-11-30 | E-MTAB-13551 | biostudies-arrayexpress
Project description:The aberrant activation of HER2 has a pivotal role in bone metastasis implantation and progression in several tumor types, in-cluding prostate cancer (PC). Trastuzumab and other anti-HER2 therapies, such as lapatinib, have been used in human breast cancer HER2 positive. Although HER2 overexpression has been reported in PC, anti-HER2 therapy response has revealed conflicting results. We investigated the potential of lapatinib in inhibiting cell migration and inducing apoptosis in two human (LNCaP and PC3) and two canine PC cell lines (PC1 and PC2). Cell migration and apoptosis were evaluated by Annexin V/PI analysis after lapatinib treatment. The transcriptome analysis of all cell lines before and after treatment with lapatinib was also performed. We found increased apoptosis and migration inhibition in LNCaP cells (androgen-sensitive cell line), while PC1, PC2, and PC3 cells showed no alterations after the treatment. The transcriptome analysis of LNCaP and PC3 cell lines showed 158 dysregulated transcripts in common, while PC1 and PC2 cell lines presented 82. At the doses of lapatinib used, we observed transcriptional modifications in all cell lines. PI3K/AKT/mTOR pathway were enriched in human PC cells, while canine PC cells showed en-richment of tyrosine kinase antitumor response and HER2-related pathways. In canine PC cells, the apoptosis failed after lapatinib treatment, possibly due to the downregulation of MAPK genes. Prostate cancer cells insensitive to androgens may be resistant to lapatinib through PI3K gene dysregulation. The association of lapatinib with PI3K inhibitors may provide a more effective anti-tumor response and clinical benefits to PC patients.
2023-11-30 | E-MTAB-13552 | biostudies-arrayexpress