Human breast cancer invasion signature
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE37733 | GEO | 2012/09/05
SECONDARY ACCESSION(S): PRJNA163099
REPOSITORIES: GEO
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Project description:Introduction: Metastasis of breast cancer is the main cause of death in patients. Previous genome-wide studies have identified gene expression patterns correlated with cancer patient outcome, however these were mostly derived from whole tissue without respect to cell heterogeneity. In reality, only a small subpopulation of migratory and invasive cells inside the primary tumor is responsible for escaping and initiating dissemination and metastasis. When whole tissue is used for molecular profiling, the expression pattern of these cells is masked by the majority of the non-invasive tumor cells. Therefore, little information is available about the crucial early steps of the metastatic cascade: migration, invasion and entry of tumor cells into the systemic circulation. Method: In the past, we have developed an in vivo invasion assay which can capture specifically the highly motile tumor cells in the act of migrating inside living tumors (Wyckoff et al., 2004, Cancer Research). Here, we used this assay in orthotopic xenografts of human MDA-MB-231 breast cancer cells to selectively isolate the invasive cell subpopulation of the primary tumor. We then performed microarray analysis to compare the gene expression profile of these invading tumor cells to the average primary tumor cells. In this way, we derived a gene signature specific to breast cancer migration and invasion in vivo. Each sample of invasive (INV) and average primary tumor cells (APTC) was pooled from two tumor-bearing mice. RNA was extracted, made into cDNA, then amplified with the Clontech SMART amplification kit. Human reference RNA (Clontech) was amplified with identifical protocol. Each sample was then hybridized in a 28K Human cDNA microarray chip, custom printed from Albert Einstein College of Medicine (http://microarray1k.aecom.yu.edu/). Four replicates were used per group (Invasive vs. Average Primary Tumor).
2012-09-05 | E-GEOD-37733 | biostudies-arrayexpress
Project description:Cell motility and invasion initiate metastasis. However, only a subpopulation of cancer cells within a tumor will ultimately become invasive. Due to this stochastic and transient nature, in an experimental setting, migrating and invading cells need to be isolated from the general population in order to study the gene expression profiles linked to these processes. This report describes microarray analysis on RNA derived from migrated or invaded subpopulations of triple negative breast cancer cells in a Transwell set-up, at two different time points during motility and invasion, pre-determined as M-bM-^@M-^\earlyM-bM-^@M-^] and M-bM-^@M-^\lateM-bM-^@M-^] in real-time kinetic assessments. Invasion- and migration-related gene expression signatures were generated through comparison with non-invasive cells, remaining at the upper side of the Transwell membranes. Late-phase signatures of both invasion and migration indicated poor prognosis in a series of breast cancer data sets. Furthermore, evaluation of the genes constituting the prognostic invasion-related gene signature revealed KruM-LM-^Hppel-like factor 9 (KLF9) as a putative suppressor of invasive growth in breast cancer. Next to loss in invasive vs non-invasive cell lines, KLF9 also showed significantly lower expression levels in the M-bM-^@M-^\earlyM-bM-^@M-^] invasive cell population, in several public expression data sets and in clinical breast cancer samples when compared to normal tissue. Overexpression of EGFP-KLF9 fusion protein significantly altered morphology and blocked invasion and growth of MDA-MB-231 cells in vitro. In addition, KLF9 expression correlated inversely with mitotic activity in clinical samples, indicating anti-proliferative effects. After selection of two time points (M-bM-^@M-^\earlyM-bM-^@M-^] and M-bM-^@M-^\lateM-bM-^@M-^]), RNA from invasive and migratory MDA-MB-231 cells was isolated from Transwell membranes and hybridized onto an Illumina HumanHT-12 v4 Expression beadchip. Gene expressions of migrated/invaded subpopulations vs non-motile cells were compared.
2014-01-29 | E-GEOD-54465 | biostudies-arrayexpress
Project description:Cell motility and invasion initiate metastasis. However, only a subpopulation of cancer cells within a tumor will ultimately become invasive. Due to this stochastic and transient nature, in an experimental setting, migrating and invading cells need to be isolated from the general population in order to study the gene expression profiles linked to these processes. This report describes microarray analysis on RNA derived from migrated or invaded subpopulations of triple negative breast cancer cells in a Transwell set-up, at two different time points during motility and invasion, pre-determined as “early” and “late” in real-time kinetic assessments. Invasion- and migration-related gene expression signatures were generated through comparison with non-invasive cells, remaining at the upper side of the Transwell membranes. Late-phase signatures of both invasion and migration indicated poor prognosis in a series of breast cancer data sets. Furthermore, evaluation of the genes constituting the prognostic invasion-related gene signature revealed Krüppel-like factor 9 (KLF9) as a putative suppressor of invasive growth in breast cancer. Next to loss in invasive vs non-invasive cell lines, KLF9 also showed significantly lower expression levels in the “early” invasive cell population, in several public expression data sets and in clinical breast cancer samples when compared to normal tissue. Overexpression of EGFP-KLF9 fusion protein significantly altered morphology and blocked invasion and growth of MDA-MB-231 cells in vitro. In addition, KLF9 expression correlated inversely with mitotic activity in clinical samples, indicating anti-proliferative effects.
2014-01-29 | GSE54465 | GEO
Project description:Breast cancer is the most common and a lethal form of cancer diagnosed in women worldwide. Although, effective treatment options for primary tumors are available, the majority of breast cancer-related deaths is caused by invasion of cells from primary tumor results in metastatic progression. Here we used a phopshoproteomic analysis to identify new targets of pro-invasive LIM kinase 2 (LIMK2) in invasive breast cancer cell lines. We show that Serine Arginine protein kinase 1 (SRPK1) is phosphorylated and activated by LIMK2 and LIMK2-SRPK1 signaling axis mediate the invasive behavior of breast cancer cells.
2020-08-31 | PXD008246 | Pride
Project description:The tumor microenvironment modifies the malignancy of tumors. In solid tumors this environment is populated by many macrophages (tumor-associated macrophages; TAMs) that in genetic studies that depleted these cells from mouse models of breast cancer were shown to promote tumor progression to malignancy and increase metastatic potential. Mechanistic studies showed that these effects are through the stimulation of tumor cell migration, invasion, intravasation as well as an enhancement of angiogenesis. Using an in vivo invasion assay it was demonstrated that invasive carcinoma cells are a unique sub-population of tumor cells whose invasion and chemotaxis is dependent upon the co-migration of TAMs with obligate reciprocal signaling through an EGF/CSF-1 paracrine loop. In this study these invasion-promoting macrophages were isolated and subjected to analysis of their transcriptome in comparison to TAMs isolated indiscriminately to function using established macrophage markers by flow cytometry. Five biological replicates for each population (Invasive and General TAM) were used.
2010-05-16 | E-GEOD-18295 | biostudies-arrayexpress
Project description:The paper describes a model of tumor invasion to bone marrow.
Created by COPASI 4.26 (Build 213)
This model is described in the article:
Modeling invasion of metastasizing cancer cells to bone marrow utilizing ecological principles
Kun-Wan Chen, Kenneth J Pienta
Theoretical Biology and Medical Modelling 2011, 8:36
Abstract:
Background: The invasion of a new species into an established ecosystem can be directly compared to the steps involved in cancer metastasis. Cancer must grow in a primary site, extravasate and survive in the circulation to then intravasate into target organ (invasive species survival in transport). Cancer cells often lay dormant at their metastatic site for a long period of time (lag period for invasive species) before proliferating (invasive spread). Proliferation in the new site has an impact on the target organ microenvironment (ecological impact) and eventually the human host (biosphere impact).
Results: Tilman has described mathematical equations for the competition between invasive species in a structured habitat. These equations were adapted to study the invasion of cancer cells into the bone marrow microenvironment as a structured habitat. A large proportion of solid tumor metastases are bone metastases, known to usurp hematopoietic stem cells (HSC) homing pathways to establish footholds in the bone marrow. This required accounting for the fact that this is the natural home of hematopoietic stem cells and that they already occupy this structured space. The adapted Tilman model of invasion dynamics is especially valuable for modeling the lag period or dormancy of cancer cells.
Conclusions: The Tilman equations for modeling the invasion of two species into a defined space have been modified to study the invasion of cancer cells into the bone marrow microenvironment. These modified equations allow a more flexible way to model the space competition between the two cell species. The ability to model initial density, metastatic seeding into the bone marrow and growth once the cells are present, and movement of cells out of the bone marrow niche and apoptosis of cells are all aspects of the adapted equations. These equations are currently being applied to clinical data sets for verification and further refinement of the models.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models .
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide.
Please refer to CC0 Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000795 | BioModels
Project description:The paper describes a model of tumor invasion to bone marrow.
Created by COPASI 4.26 (Build 213)
This model is described in the article:
Modeling invasion of metastasizing cancer cells to bone marrow utilizing ecological principles
Kun-Wan Chen, Kenneth J Pienta
Theoretical Biology and Medical Modelling 2011, 8:36
Abstract:
Background: The invasion of a new species into an established ecosystem can be directly compared to the steps involved in cancer metastasis. Cancer must grow in a primary site, extravasate and survive in the circulation to then intravasate into target organ (invasive species survival in transport). Cancer cells often lay dormant at their metastatic site for a long period of time (lag period for invasive species) before proliferating (invasive spread). Proliferation in the new site has an impact on the target organ microenvironment (ecological impact) and eventually the human host (biosphere impact).
Results: Tilman has described mathematical equations for the competition between invasive species in a structured habitat. These equations were adapted to study the invasion of cancer cells into the bone marrow microenvironment as a structured habitat. A large proportion of solid tumor metastases are bone metastases, known to usurp hematopoietic stem cells (HSC) homing pathways to establish footholds in the bone marrow. This required accounting for the fact that this is the natural home of hematopoietic stem cells and that they already occupy this structured space. The adapted Tilman model of invasion dynamics is especially valuable for modeling the lag period or dormancy of cancer cells.
Conclusions: The Tilman equations for modeling the invasion of two species into a defined space have been modified to study the invasion of cancer cells into the bone marrow microenvironment. These modified equations allow a more flexible way to model the space competition between the two cell species. The ability to model initial density, metastatic seeding into the bone marrow and growth once the cells are present, and movement of cells out of the bone marrow niche and apoptosis of cells are all aspects of the adapted equations. These equations are currently being applied to clinical data sets for verification and further refinement of the models.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models .
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide.
Please refer to CC0 Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000793 | BioModels
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:It has been suggested that breast cancers are driven and maintained by a cellular subpopulation with stem cell properties. These breast cancer stem cells (BCSCs) mediate metastasis and by virtue of their resistance to radiation and chemotherapy, contribute to relapse. Although several BCSC markers have been described, it is unclear whether these markers identify the same or independent BCSC populations. Based on established breast cancer cell lines, as well as primary tumor xenografts, we show that BCSCs exist in distinct mesenchymal-like (epithelial-mesenchymal transition, EMT) and epithelial-like (mesenchymal-epithelial transition, MET) states characterized by expression of distinct markers, proliferative capacity and invasive characteristics. The gene expression profiles of mesenchymal-like and epithelial-like BCSCs are remarkably similar across the different molecular subtypes of breast cancer and resemble those of distinct basal and luminal stem cells found in the normal breast. We propose that the plasticity of BCSCs allowing them to transition between EMT- and MET-like states endows these cells with the capacity for tissue invasion, dissemination and growth at metastatic sites. Breast cancer cell lines, primary xenografts and normal breast cells from patient were sorted using flow cytometry to select for cells that were CD24-,CD44+ and ALDH+. Gene expression profiles of CD24-CD44+ cells were compared with non-CD24-CD44+ cells. Gene expression profiles of ALDH+ cells were compared with ALDH- cells.
2013-11-13 | E-GEOD-52262 | biostudies-arrayexpress
Project description:It has been suggested that breast cancers are driven and maintained by a cellular subpopulation with stem cell properties. These breast cancer stem cells (BCSCs) mediate metastasis and by virtue of their resistance to radiation and chemotherapy, contribute to relapse. Although several BCSC markers have been described, it is unclear whether these markers identify the same or independent BCSC populations. Based on established breast cancer cell lines, as well as primary tumor samples and xenografts, we show that BCSCs exist in distinct mesenchymal-like (epithelial-mesenchymal transition, EMT) and epithelial-like (mesenchymal-epithelial transition, MET) states characterized by expression of distinct markers, proliferative capacity and invasive characteristics. The gene expression profiles of mesenchymal-like and epithelial-like BCSCs are remarkably similar across the different molecular subtypes of breast cancer and resemble those of distinct basal and luminal stem cells found in the normal breast. We propose that the plasticity of BCSCs allowing them to transition between EMT- and MET-like states endows these cells with the capacity for tissue invasion, dissemination and growth at metastatic sites. Breast cancer cells from patient were sorted using flow cytometry to select for cells that were ALDH+. Gene expression profiles of these cells were compared with profiles of ALDH- cells.
2013-11-14 | E-GEOD-52327 | biostudies-arrayexpress