Project description:A major problem in cancer research is the lack of a tractable model for delayed metastasis. Herein we show that cancer cells suppressed by SISgel, a gel-forming normal ECM material derived from Small Intestine Submucosa, in flank xenografts show properties of suppression and re-activation that are very similar to normal delayed metastasis and suggest they can serve as a novel model for developing therapeutics to target micrometastases or suppressed cancer cells. Co-injection with SISgel suppressed the malignant phenotype of highly invasive J82 and T24 bladder cancer cells and highly metastatic JB-V cells in flank xenografts. Cells could remain viable up to 120 days without forming tumors and appeared much more highly differentiated and less atypical than tumors from cells co-injected with Matrigel. In 40% of SISgel xenografts, growth resumed in the malignant phenotype after a period of suppression or dormancy for at least 30 days and was more likely with implantation of 3 million cells or more cells. Ordinary Type I collagen did not suppress malignant growth, and tumors developed about as well with collagen as with Matrigel. A clear signal in gene expression over different cell lines was not seen, but in contrast, Reverse Phase Protein Analysis of 250 proteins across 4 cell lines identified a clear signal at the protein level involving Integrin Linked Kinase (ILK) signaling that was confirmed by an ILK inhibitor. We suggest that cancer cells suppressed on SISgel could serve as a model for dormancy and re-awakening to develop therapeutic targets for micrometastases. Earlier we demonstrated that the phenotype of bladder cancer cells was radically different in 3-dimensional organotypic culture when grown on a normal extracellular matrix preparation (SISgel) as compared to that observed on a cancer-modulated permissive extracellular matrix preparation (Matrigel). SISgel is a gel-forming material derived from acellular small intestine submucosa, whereas Matrigel is a basement membrane preparation obtained from a mouse sarcoma. On Matrigel the bladder cancer cells recapitulated the phenotype reported for the original tumor; in sharp contrast, most of the malignant properties were lost when the cells were grown on SISgel. Cell lines derived from papillomas formed a layered structure reminiscent of normal urothelium, whereas cell lines derived from higher grade tumors formed a noninvasive layer of cells. These findings suggested that growth of cancer cells on normal ECM could provide a model to investigate the phenomenon of suppression of malignancy by normal ECM in metastasis and recurrence. In this study we explored whether the phenotypic suppression seen in organotypic culture of bladder cancer cells on SISgel also is observed in vivo. Positive findings support the use of SISgel as a model for investigations of the dormant or suppressed tumor cell phenotype and of mechanisms by which the normal ECM exerts an inhibitory influence on tumorigenesis and metastasis. The findings strongly suggest that interactions of cancer cells with normal ECM play an important role in recurrence and metastasis and further suggest that targeting suppressed cells could represent a heretofore unexploited point of vulnerability in cancer therapy.

Project description:The study demonstrated the gene expression through microarray analysis of total mRNA in rams experimentally infected with a rough (R) virulent strain of Brucella ovis in reproductive organs (epididymus, testicles, ampolae, vesicular glands, bulbourethral glands) and a pool of lymph nodes (inguinal and scrotal) at three different times: acute phase (60 days post challenge [dpc]), chronic phase 1 (120dpc), and chronic phase 2 (240dpc) of infection. To further define the gene expression changes associated with infected rams, the profiles of a control group (0 dpc) of rams was compared using the Affymetrix Bovine Genome Array. Of the 23,000 genes that were analyzed on the array, B. ovis infection in rams’ tissues revealed 139, 930 and 744 Differentially Expressed Genes (DEGs) in the acute, chronic 1, and chronic phase 2 of infection, respectively. Among the three phases of infection, 44 DEGs (30 known and 14 unknown genes) were expressed in common. The biological functions of immune cell trafficking, immunological disease, infectious disease, inflammatory disease, inflammatory response and cellular movement were significant at the three phases of infection. The results support the first microarray analysis of ram tissues infected with an R strain of B. ovis. A total of twelve 12-month-old healthy Santa Inês rams, previously diagnosed as negative for brucellosis/visna maedi/toxoplasmosis/neosporosis, were selected for the study. The rams were kept in an isolated pen and experimentally challenged with a rough (R) virulent B. ovis PA strain (ATCC 25840). For the experiment, the rams were classified during the course of infection according to time: 0 dpc (control), 60 dpc (acute phase), 120 dpc (chronic phase 1) and 240 dpc (chronic phase 2). For each time, the tissues epididymus, testicles, ampolae, vesicular glands, bulbourethral glands, and a pool of lymph nodes (inguinal and scrotal) were collected. Three rams were euthanized and necropsied for tissues collection purposes for each time. To define the gene expression changes associated with infected rams, the profile of a control group (0 dpc) of rams was compared using microarray technology. REPLACE This dataset includes control samples and acute phase samples.

Project description:The study demonstrated the gene expression through microarray analysis of total mRNA in rams experimentally infected with a rough (R) virulent strain of Brucella ovis in reproductive organs (epididymus, testicles, ampolae, vesicular glands, bulbourethral glands) and a pool of lymph nodes (inguinal and scrotal) at three different times: acute phase (60 days post challenge [dpc]), chronic phase 1 (120dpc), and chronic phase 2 (240dpc) of infection. To further define the gene expression changes associated with infected rams, the profiles of a control group (0 dpc) of rams was compared using the Affymetrix Bovine Genome Array. Of the 23,000 genes that were analyzed on the array, B. ovis infection in rams’ tissues revealed 139, 930 and 744 Differentially Expressed Genes (DEGs) in the acute, chronic 1, and chronic phase 2 of infection, respectively. Among the three phases of infection, 44 DEGs (30 known and 14 unknown genes) were expressed in common. The biological functions of immune cell trafficking, immunological disease, infectious disease, inflammatory disease, inflammatory response and cellular movement were significant at the three phases of infection. The results support the first microarray analysis of ram tissues infected with an R strain of B. ovis. A total of twelve 12-month-old healthy Santa Inês rams, previously diagnosed as negative for brucellosis/visna maedi/toxoplasmosis/neosporosis, were selected for the study. The rams were kept in an isolated pen and experimentally challenged with a rough (R) virulent B. ovis PA strain (ATCC 25840). For the experiment, the rams were classified during the course of infection according to time: 0 dpc (control), 60 dpc (acute phase), 120 dpc (chronic phase 1) and 240 dpc (chronic phase 2). For each time, the tissues epididymus, testicles, ampolae, vesicular glands, bulbourethral glands, and a pool of lymph nodes (inguinal and scrotal) were collected. Three rams were euthanized and necropsied for tissues collection purposes for each time. To define the gene expression changes associated with infected rams, the profile of a control group (0 dpc) of rams was compared using microarray technology. REPLACE This dataset includes control samples and chronic 1 phase samples.

Project description:The study demonstrated the gene expression through microarray analysis of total mRNA in rams experimentally infected with a rough (R) virulent strain of Brucella ovis in reproductive organs (epididymus, testicles, ampolae, vesicular glands, bulbourethral glands) and a pool of lymph nodes (inguinal and scrotal) at three different times: acute phase (60 days post challenge [dpc]), chronic phase 1 (120dpc), and chronic phase 2 (240dpc) of infection. To further define the gene expression changes associated with infected rams, the profiles of a control group (0 dpc) of rams was compared using the Affymetrix Bovine Genome Array. Of the 23,000 genes that were analyzed on the array, B. ovis infection in rams’ tissues revealed 139, 930 and 744 Differentially Expressed Genes (DEGs) in the acute, chronic 1, and chronic phase 2 of infection, respectively. Among the three phases of infection, 44 DEGs (30 known and 14 unknown genes) were expressed in common. The biological functions of immune cell trafficking, immunological disease, infectious disease, inflammatory disease, inflammatory response and cellular movement were significant at the three phases of infection. The results support the first microarray analysis of ram tissues infected with an R strain of B. ovis. A total of twelve 12-month-old healthy Santa Inês rams, previously diagnosed as negative for brucellosis/visna maedi/toxoplasmosis/neosporosis, were selected for the study. The rams were kept in an isolated pen and experimentally challenged with a rough (R) virulent B. ovis PA strain (ATCC 25840). For the experiment, the rams were classified during the course of infection according to time: 0 dpc (control), 60 dpc (acute phase), 120 dpc (chronic phase 1) and 240 dpc (chronic phase 2). For each time, the tissues epididymus, testicles, ampolae, vesicular glands, bulbourethral glands, and a pool of lymph nodes (inguinal and scrotal) were collected. Three rams were euthanized and necropsied for tissues collection purposes for each time. To define the gene expression changes associated with infected rams, the profile of a control group (0 dpc) of rams was compared using microarray technology. REPLACE This dataset includes control samples and chronic 2 phase samples.

Dataset Information

RNAi profiling by array of human MCF7 cells with siRNA-mediated knockdown of CNOT6 and/or CNOT6L, or CNOT7 and CNOT8

Publications

The Ccr4a (CNOT6) and Ccr4b (CNOT6L) deadenylase subunits of the human Ccr4-Not complex contribute to the prevention of cell death and senescence.

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