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Project description:Description of molecular changes of prostate cancer cells with increased in vivo metastatic potential compared to parental tumor cells
2021-12-29 | GSE86642 | GEO
Project description:Description of molecular changes of prostate cancer cells with increased in vivo metastatic potential
2021-12-29 | GSE86916 | GEO
Project description:Expression data from PC-3 cells with increased in vivo metastatic potential compared to parental tumor cells
| PRJNA342958 | ENA
Project description:Prostate cancer (PCa) is the second most frequently diagnosed cancer and the fifth leading cause of death from cancer in men worldwide. Increased understanding of the prostate cancer metastasis mechanisms will help identify more efficient intervention strategies to prevent or treat this deadly disease in the future. To identify the candidate proteins that contribute to metastasis of PCa, isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis was performed to explore differentially expressed proteins between two homologous human prostate cancer cell lines including highly-metastatic PC-3M-1E8 cell line and poorly-metastatic PC-3M-2B4 cell line. Here, a total of 58 proteins were identified to be significantly differentially expressed between PC-3M-1E8 and PC-3M-2B4 cells, which were further verified using real-time quantitative PCR and western blot analysis. The bioinformatic analysis suggested that the differentially expressed proteins, like MMP1 and FHL1, may contribute to the higher metastatic ability of PC-3M-1E8 cells than PC-3M-2B4 cells. In addition, functional analyses proved MMP1's positive effect on the higher metastatic ability of PC-3M-1E8 cells than PC-3M-2B4 cells. These findings provided a unique resource to specifically reveal the complex molecular regulatory mechanisms underlying the progression of prostate cancer from poorly-metastatic to highly-metastatic stage.
| S-EPMC6209233 | biostudies-literature
Project description:Photodynamic therapy (PDT) is an emerging treatment for malignant and inflammatory dermal disorders. Photoirradiation of the silicon phthalocyanine (Pc) 4 photosensitizer with red light generates singlet oxygen and other reactive oxygen species to induce cell death. We previously reported that Pc 4-PDT elicited cell death in lymphoid-derived (Jurkat) and epithelial-derived (A431) cell lines in vitro, and furthermore that Jurkat cells were more sensitive than A431 cells to treatment. In this study, we examined the effectiveness of Pc 4-PDT on primary human CD3(+) T cells in vitro. Fluorometric analyses of lysed T cells confirmed the dose-dependent uptake of Pc 4 in non-stimulated and stimulated T cells. Flow cytometric analyses measuring annexin V and propidium iodide (PI) demonstrated a dose-dependent increase of T cell apoptosis (6.6-59.9%) at Pc 4 doses ranging from 0-300 nM. Following T cell stimulation through the T cell receptor using a combination of anti-CD3 and anti-CD28 antibodies, activated T cells exhibited increased susceptibility to Pc 4-PDT-induced apoptosis (10.6-81.2%) as determined by Pc 4 fluorescence in each cell, in both non-stimulated and stimulated T cells, Pc 4 uptake increased with Pc 4 dose up to 300 nM as assessed by flow cytometry. The mean fluorescence intensity (MFI) of Pc 4 uptake measured in stimulated T cells was significantly increased over the uptake of resting T cells at each dose of Pc 4 tested (50, 100, 150 and 300 nM, p < 0.001 between 50 and 150 nM, n = 8). Treg uptake was diminished relative to other T cells. Cutaneous T cell lymphoma (CTCL) T cells appeared to take up somewhat more Pc 4 than normal resting T cells at 100 and 150 nm Pc 4. Confocal imaging revealed that Pc 4 localized in cytoplasmic organelles, with approximately half of the Pc 4 co-localized with mitochondria in T cells. Thus, Pc 4-PDT exerts an enhanced apoptotic effect on activated CD3(+) T cells that may be exploited in targeting T cell-mediated skin diseases, such as cutaneous T cell lymphoma (CTCL) or psoriasis.
| S-EPMC4928582 | biostudies-literature
Project description:BACKGROUND: Mesenchymal and amoeboid movements are two important mechanisms adopted by cancer cells to invade the surrounding environment. Mesenchymal movement depends on extracellular matrix protease activity, amoeboid movement on the RhoA-dependent kinase ROCK. Cancer cells can switch from one mechanism to the other in response to different stimuli, limiting the efficacy of antimetastatic therapies. METHODOLOGY AND PRINCIPAL FINDINGS: We investigated the acquisition and molecular regulation of the invasion capacity of neoplastically transformed human fibroblasts, which were able to induce sarcomas and metastases when injected into immunocompromised mice. We found that neoplastic transformation was associated with a change in cell morphology (from fibroblastic to polygonal), a reorganization of the actin cytoskeleton, a decrease in the expression of several matrix metalloproteases and increases in cell motility and invasiveness. In a three-dimensional environment, sarcomagenic cells showed a spherical morphology with cortical actin rings, suggesting a switch from mesenchymal to amoeboid movement. Accordingly, cell invasion decreased after treatment with the ROCK inhibitor Y27632, but not with the matrix protease inhibitor Ro 28-2653. The increased invasiveness of tumorigenic cells was associated with reduced expression of Rnd3 (also known as RhoE), a cellular inhibitor of ROCK. Indeed, ectopic Rnd3 expression reduced their invasive ability in vitro and their metastatic potential in vivo. CONCLUSIONS: These results indicate that, during neoplastic transformation, cells of mesenchymal origin can switch from a mesenchymal mode of movement to an amoeboid one. In addition, they point to Rnd3 as a possible regulator of mesenchymal tumor cell invasion and to ROCK as a potential therapeutic target for sarcomas.
| S-EPMC3014295 | biostudies-literature
Project description:The dissemination of circulating tumor cells (CTCs) by lymph fluid is one of the key events in the development of tumor metastasis. However, little progress has been made in studying lymphatic CTCs (L-CTCs). Here, we demonstrate the detection of L-CTCs in preclinical mouse models of melanoma and breast cancer using in vivo high-sensitivity photoacoustic and fluorescent flow cytometry. We discovered that L-CTCs are be detected in pre-metastatic disease stage. The smallest primary tumor that shed L-CTCs was measured as 0.094mm×0.094mm, its volume was calculated as 0.0004 mm3; and its productivity was estimated as 1 L-CTC per 30 minutes. As the disease progressed, primary tumors continued releasing L-CTCs with certain individual dynamics. The integrated assessment of lymph and blood underlined the parallel dissemination of CTCs at all disease stages. However, the analysis of links between L-CTC counts, blood CTC (B-CTC) counts, primary tumor size and metastasis did not reveal statistically significant correlations, likely due to L-CTC heterogeneity. Altogether, our results showed the feasibility of our diagnostic platform using photoacoustic flow cytometry for preclinical L-CTC research with translational potential. Our findings also demonstrated new insights into lymphatic system involvement in CTC dissemination. They help to lay the scientific foundation for the consideration of L-CTCs as prognostic markers of metastasis and to emphasize the integrative assessment of lymph and blood.
| S-EPMC7650582 | biostudies-literature
Project description:Recent studies have demonstrated that the chemokine receptor CXCR4 plays a crucial role in organ-specific metastasis formation. Although a variety of studies showed the expression of chemokine receptors, in particular, CXCR4, by gastrointestinal tumors, the precise mechanisms of chemokine receptor-mediated homing of cancer cells to specific sites of metastasis remained elusive. Here, we used liver metastatic human HEP-G2 hepatoma and HT-29LMM colon cancer cells expressing functional CXCR4 to dissect the metastatic cascade by intravital fluorescence microscopy. Immunohistochemistry revealed that the CXCR4 ligand CXCL12 is expressed by endothelial cells and likely Kupffer cells lining the liver sinusoids. Tumor cell adhesion and extravasation in vivo was quantitatively analyzed using intravital fluorescence microscopy. Treatment of cells with an anti-CXCR4 antibody did not affect cell adhesion but significantly impaired tumor cell extravasation (HEP-G2; isotype control: 22.3% +/- 4.3% vs anti-CXCR4: 6.0% +/- 5.0%, P < .001). In addition, pretreatment of tumor cells with the ligand CXCL12 enhanced the activation of the small GTPases Rho, Rac, and cdc42 as well as tumor cell extravasation without affecting tumor cell adhesion within liver sinusoids. Taken together, the findings of the present study provide first in vivo insights into the early events of chemokine ligand/receptor-mediated liver metastasis formation of tumor cells and define tumor cell extravasation rather than tumor cell arrest as the rate-limiting event.
| S-EPMC2697351 | biostudies-literature
Project description:The prognosis of metastatic osteosarcoma (OS) remains poor with a <20% survival rate, particularly in cases of distant (non-lung) metastases. Tumor-treating field (TTF) therapy is a novel electric field-based treatment that causes metaphase arrest and tumor cell death, with the advantage of reduced side effects compared to radiation and chemotherapy. TTF shows promise in glioblastoma and other solid tumors; however, few studies have examined its potential in the treatment of osteosarcoma. Therefore, we explored the mechanism of TTF-induced metastasis inhibition and cell death using in vitro models. TTF (1.5 V/cm, 150 kHz) was applied to U2OS and KHOS/NP OS cell lines. In addition, a 3-dimensional culture system was established using these OS cell lines. Cell migration and invasion (i.e., metastatic potential) were examined using a wound-healing scratch assay and transwell assay, respectively. Western blotting of metastasis- and angiogenesis-related proteins was performed. TTF suppressed the migration of and invasion by OS cells and inhibited the expression of epithelial markers, thereby preventing epithelial-mesenchymal transition (EMT), a hallmark of metastasis. Moreover, TTF prevented angiogenesis in human tumor endothelial cells and downregulated matrix metalloproteinase-2 (MMP2) and vascular endothelial growth factor (VEGF) expression. Therefore, TTF shows potential as an improved treatment for osteosarcoma, warranting further preclinical studies in animal models to support clinical trials.
| S-EPMC7502799 | biostudies-literature
Project description:<p>Circulating tumor cells (CTCs) are recognized as direct seeds of metastasis. However, CTC count may not be the 'best' indicator of metastatic risk because their heterogeneity is generally neglected. In this study, we develop a molecular typing system to predict colorectal cancer metastasis potential based on the metabolic fingerprints of single CTCs. After identification of the metabolites potentially related to metastasis using mass spectrometry-based untargeted metabolomics, setup of a home-built single-cell quantitative mass spectrometric platform for target metabolite analysis in individual CTCs and use of a machine learning method composed of non-negative matrix factorization and logistic regression, CTCs are divided into two subgroups, C1 and C2, based on a 4-metabolite fingerprint. Both <em>in vitro</em> and <em>in vivo</em> experiments demonstrate that CTC count in C2 subgroup is closely associated with metastasis incidence. This is an interesting report on the presence of a specific population of CTCs with distinct metastatic potential at the single-cell metabolite level. </p>
2023-08-21 | MTBLS5028 | MetaboLights