Comparison of gene expression profile between primary and bone metastasized cancers
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PROVIDER: PRJNA915936 | ENA |
REPOSITORIES: ENA
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Project description:Bone metastasis occurs frequently in cancer patients. Conventional therapies have limited therapeutic outcomes, and thus, exploring the mechanisms of cancer progression in the bone metastasis is important to develop new effective therapies. In the bone microenvironment, adipocytes are the major stromal cells that interact with cancer cells during the bone metastasis. However, the comprehensive functions of bone marrow adipocytes in cancer progression are not yet fully understood. To address this, we investigated the role of bone marrow adipocytes on cancer cells, by focusing on an invasive front which reflects the direct effects of stromal cells on caner. In comprehensive histopathological and genetic analysis using bone metastasis specimens, we examined invasive fronts in bone metastasis and compared invasive fronts with adipocyte-rich bone marrow (adipo-BM) to those with hematopoietic cell-rich bone marrow (hemato-BM) as a normal counterpart of adipocytes. We found morphological complexity of invasive front with adipo-BM was significantly higher than that with hemato-BM. Based on immunohistochemistry, the invasive front with adipo-BM comparatively had significantly increased cancer-associated fibroblasts (CAFs) marker-positive area and lower density of CD8 positive lymphocytes compared to that with hemato-BM. RNA-seq analysis of primary and bone metastasis cancer reveals that bone metastasized cancer cells acquired drug resistance related gene expression phenotypes. Clearly, these findings indicate that bone marrow adipocytes provide favorable tumor microenvironment for cancer invasion and therapeutic resistance of bone metastasized cancers via CAF induction and immune evasion, providing a potential target for the treatment of bone metastasis.
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Project description:Comparison of genomic alterations of primary colorectal cancers with liver metastases of the same patient Keywords: array CGH, colorectal cancer, colon cancer, liver metastasis
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Project description:Comparison of expression profiles of primary colorectal cancers with liver metastases of the same patient. Additionally, expression data of normal colon and liver tissue. Abstract of publication will be included upon publication Keywords: expression profiling, colorectal cancer, colon cancer, liver metastasis, normal colonic tissue, normal liver tissue
2010-07-07 | GSE14297 | GEO
Project description:Comparison of expression profiles of primary colorectal cancers with liver metastases of the same patient. Additionally, expression data of normal colon and liver tissue. Abstract of publication will be included upon publication Keywords: expression profiling, colorectal cancer, colon cancer, liver metastasis, normal colonic tissue, normal liver tissue RNA of 18 primary colorectal cancers, 18 matched liver metastases, 7 normal colon epithelium samples and 5 normal liver tissue samples hybridized on Human Sentrix-6 V2 (Illumina)
2010-07-07 | E-GEOD-14297 | biostudies-arrayexpress
Project description:Breast cancer metastasis to bone is a critical determinant of long-term survival after treatment of primary tumors. We used a mouse model of spontaneous bone metastasis to determine new molecular mechanisms. Differential transcriptome comparisons of primary and metastatic tumor cells revealed that a substantial set of genes suppressed in bone metastases were highly enriched for promoter elements for the type I interferon (IFN) regulatory factor, Irf7, itself suppressed in mouse and human metastases. The critical function of the Irf7 pathway was demonstrated by restoration of exogenous Irf7 or systemic interferon administration, which significantly reduced bone metastases and prolonged metastasis-free survival. Using mice deficient in the type I receptor (Ifnar1-/-) or mature B, T and NK cell responses (NOD Scid IL-2rγ-/- mice), we demonstrated that Irf7-driven suppression of metastasis was reliant on IFN signaling to host immune cells. Metastasis suppression correlated with decreased accumulation of myeloid-derived suppressor cells and increased CD4++, CD8 T cells and NK cells in the peripheral blood and was reversed by depletion of CD8+ cells and NK cells. Clinical importance of our findings was demonstrated as increased primary tumor Irf7 expression predicted prolonged bone and lung metastasis-free survival. Thus we report for the first time, a novel innate immune pathway, intrinsic to breast cancer cells, whose suppression in turn restricts systemic immunosurveillance to enable metastasis. This pathway may constitute a novel therapeutic target for restricting breast cancer metastases. Microarrays were used to profile transcriptional alterations inherent in tumor cells growing in bone when compared to matched primary tumor cells in the 4T1.2 murine mammary tumor model. Primary and metastasized tumor were isolated from the same mouse with 4 independent biological replicates.
2012-07-17 | E-GEOD-37975 | biostudies-arrayexpress
Project description:We used here the presence of disseminated tumors cells (DTC) in the bone marrow for defining early metastasized breast cancer patients. By comparing expression profiles of early metastasized primary breast tumors with non-metastasized tumors, we found candidate metastasis suppressor genes that were further validated in other published breast cancer data.
2015-04-01 | E-MTAB-2501 | biostudies-arrayexpress
Project description:Recently, there is increasing report of bone necrosis exceptionally in jaw bone areas after long term administration of anti-resorptive agent, bisphosphonate (BP). It is still unknown that why BP does not result in osteonecrosis but potentiate fracture repair in axial skeleton such as long bones. Many reports had shown that mandibular bone or calvarial bone exhibits lesser resoption than iliac bone graft for maxillofacial bone defect.(Jackson et al 1986, Koole et al 1989),(Crespi et al 2007) These might be attributed to the embryological difference between the two different type of the bone; intramembranous versus endochondral bone formation. Maxilla and mandibular alveolar and basal bone are originated from neural crest cells and exhibit intramembranous bone formation.(Chai and Maxson 2006) However, axial skeleton such as iliac or tibial bones are originated from mesoderm and undergo endochondral bone formation.(Helms and Schneider 2003) It had been reported that there is distinct phenotype difference in human bone cells from different skeletal origin.(Akintoye et al 2006, Kasperk et al 1997),(Matsubara et al 2005) Akintoye et al.(Akintoye et al 2006) reported that mandibular bone marrow stromal cells (BMSCs) displayed a fibroblast-like morphology similar to iliac BMSCs in histological appearance. However, mandibular bone contained less red marrow and hematopoietic cells, whereas the iliac bone contained more red marrow thereby contributing more to hematopoiesis. This differential capacity of mandibular BMSCs with less hematopoietic stem cells is better than that of iliac BMSCs because mitosis in hematopoietic stem cells is usually stopped. They also reported that maxillofacial BMSCs shows higher proliferation rate and alkaline phosphotase activity.(Akintoye et al 2006, Akintoye et al 2008) However, in vivo response of human BMSCs to osteogenic induction was higher in iliac bone than maxillomandibular bone.(Akintoye et al 2006) Other reports had shown that BMSCs from mandible showed better in vitro and in vivo bone formation capacity compared to tibia from rats.(Aghaloo et al 2010) Matsubara et al. reported that osteogenic potential of human or canine alveolar bone and iliac bone-derived cells (BC) are similar but showed difference in chondrogenic and adipogenic potential.(Matsubara et al 2005) From the previous studies, the site-related difference of mandibular and iliac BC are clear. However, the pattern of the site-specificity are not exactly same among above mentioned studies. These might be attributed to the difference in the experimental subjects (species, age) and study design (in-patient or random comparison, etc). Moreover, underlying genetic mechanism of these skeletal-site dependent difference had not been fully investigated. The investigation of site-specific differences in the gene expression would be help to understand the mechanism of bisphosphonate-related osteonecrosis of the jaw (BRONJ), which recently has become an major issue in dentistry. Considering that bisphosphonate is frequently prescribed to elderly patients who have a higher risk of osteoporosis, it is necessary to conduct a experimental analysis of cells from older-aged donors. It had been suggested that anatomical site-specific difference can be influenced by 1) difference in the regional blood supply, 2) difference in bone composition (lamellar bone versus trabecular bone), 3) difference in physiological strain exerted to bone, 4) difference in gene expression according to skeletal site.(Kasperk et al 1997) In this study, bone cells derived from elderly donors went through microarray analysis under the hypothesis that there would be the differences in gene expressions involved in bone formation or cell proliferation of bone cells from iliac and mandible. The purpose of this study was to investigate the difference in gene expression between the human mandible and iliac bone so that we can understand the genetic difference in the two different type of bones. <<<References>>> 1. Jackson IT, Helden G, Marx R. Skull bone grafts in maxillofacial and craniofacial surgery. J Oral Maxillofac Surg 1986; 44:949-955. 2. Koole R, Bosker H, van der Dussen FN. Late secondary autogenous bone grafting in cleft patients comparing mandibular (ectomesenchymal) and iliac crest (mesenchymal) grafts. J Craniomaxillofac Surg 1989; 17 Suppl 1:28-30. 3. Crespi R, Vinci R, Cappare P, Gherlone E, Romanos GE. Calvarial versus iliac crest for autologous bone graft material for a sinus lift procedure: a histomorphometric study. Int J Oral Maxillofac Implants 2007; 22:527-532. 4. Chai Y, Maxson RE, Jr. Recent advances in craniofacial morphogenesis. Dev Dyn 2006; 235:2353-2375. 5. Helms JA, Schneider RA. Cranial skeletal biology. Nature 2003; 423:326-331. 6. Kasperk C, Helmboldt A, Borcsok Iet al. Skeletal site-dependent expression of the androgen receptor in human osteoblastic cell populations. Calcif Tissue Int 1997; 61:464-473. <<< Important Abstract of Associated reference>>> Kingsmill VJ1, McKay IJ, Ryan P, Ogden MR, Rawlinson SC. Gene expression profiles of mandible reveal features of both calvarial and ulnar bones in the adult rat.J Dent. 2013 Mar;41(3):258-64. doi: 10.1016/j.jdent.2012.11.010. Epub 2012 Nov 23. OBJECTIVES: Limb and mandibular alveolar bone of the mandible are susceptible to disuse osteopenia, whilst skull and mandibular basal bone appear to resist excessive generalised bone loss. We wanted to compare the site-specific transcriptome of anatomically and functionally distinct bones to confirm the composite nature of the mandible at the molecular level. METHODS: Gene expression profiles were obtained for the mandible, ulna, and calvaria of adult male rats using Affymetrix Rat Genome 230 2.0 GeneChips. Ingenuity Pathways Assist generated association maps, and RGD database software identified site-specific pathways. RESULTS: The majority of expressed transcripts (84%) are common to all three sites. The mandible expressed 873 transcripts in common with ulna but not calvaria, and 1014 transcripts in common with calvaria but not ulna. Transcripts in these groups were excluded if they showed significant differential expression (>2-fold) and the remaining mapped genes were filtered for those related to modulation of gene transcription. Analysis of these genes revealed common pathways shared by the mandible and ulna, or mandible and calvaria, which were not shared by the calvaria and ulna. CONCLUSIONS: There were relatively few differences in the expression of genes responsible for the bone formation process per se in different functional skeletal sites. Differential transcription factor expression suggests that it is the regulation of bone formation and not the mechanism of bone formation itself that differs between the skeletal sites. CLINICAL SIGNIFICAN Objectives: The exact genetic difference between the jaw and long bone had not been clearly understood. The purpose of this study was to investigate the difference in gene expression between the human mandible and iliac bone-derived cells. Methods: Primary cells were obtained from mandibular and iliac bone from the 6 healthy, elderly donors (average age 60.2 years) during the reconstruction of mandibular alveolar bone defects. To investigate site-specific difference, within-patient comparison were carried out with cell proliferation and osteoblastic differentiation assay. Gene expression profile of mandible and iliac BC (bone-derived cell) were compared using cDNA microarray analysis using Affymetrix GeneChip®. Results: The mandibular BC showed stronger proliferative capacity but weaker osteoblastic differentiation. The comparison of the gene expression profile identified that 82 genes were significantly up-regulated and 66 genes were down-regulated 1.5 fold or greater in mandible compared to iliac BC. The most significantly differentially regulated genes were associated with skeletal system development and morphogenesis (SIX1, MSX1, MSX2, HAND2, PRRX1, OSR2, HOX gene family, PITX2). Microarray analysis revealed that Msx1 was 2.03 fold and Msx2 was 1.99 fold up-regulated in mandible compared to iliac BC (both p<0.01). HOX gene group in mandibular BC was down-regulated (p<0.01). Osteopontin was also 2.84 fold down-regulated in mandible BC (p<0.01). We found that the results of the microarray were reproducible with qRT-PCR. Conclusions: Site-specific difference between jaw and long bone can be explained by the different gene expression pattern, which is primarily related with embryological origin of these two different bones.
2014-06-14 | GSE58474 | GEO
Project description:Genetic of multiple primary cancers
| PRJNA1131824 | ENA
Project description:iRFP713-lebeled iCSCL-10A cells were injected into immunodeficient mice. 5 weeks later, bone metastasized iCSCL-10A cells were extracted from bone marrow was compared with injected cell in vitro culture by microarray and pathway analysis.
2020-05-31 | GSE114942 | GEO