Primary sclerosing epithelioid fibrosarcoma (SEF) of bone is a rare and scarcely reported neoplasm. We document clinicopathological and molecular features of 9 additional cases. Five males and 4 females had a mean age of 39 years (14-71 years). Most tumors affected flat/irregular bones; only 3 cases involved a long bone. By radiology, it has characteristic radiographic features of a predominantly lytic expansile lesion with a sclerotic rim. Referring diagnoses were SEF (n = 2), low-grade osteosarcoma (n = 2), chondrosarcoma (n = 1), and chondromyxoid fibroma (n = 1). Histologically, five cases revealed classical morphology of SEF of soft tissue. Remaining cases were classified as hybrid SEF/low-grade fibromyxoid sarcoma, characterized by spindle or stellate cells, prominent stroma, and giant hyalinized areas. Various morphological deviations such as prominent vasculature (n = 3), osteoid-like material (n = 4), or parallel bone trabeculae (n = 2) were observed. Immunohistochemically, all cases showed diffuse and strong MUC4 expression. SATB2 was observed in 5/8 cases. Using FISH, EWSR1, and FUS rearrangements were detected in 4 cases and 1 case, respectively. EWSR1-CREB3L1 fusion was identified in 1 additional case by next-generation sequencing. Recurrence and metastasis were observed in 1 case and 2 cases, respectively. All but one patient were alive with disease for a mean interval of 31 months. SEF of bone is a relatively indolent sarcoma of adults, most commonly located in the flat/irregular bones. Due to overlapping histological features, it is often misdiagnosed as osteosarcoma or a chondroid tumor. Most SEF of bone exhibit EWSR1 rearrangements, but rare cases may harbor a FUS gene fusion.

• MeSH
• Adult MeSH
• Phenotype MeSH
• Fibrosarcoma diagnosis   genetics   metabolism   pathology   MeSH
• Gene Rearrangement MeSH
• Immunohistochemistry MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Recurrence, Local diagnosis   genetics   metabolism   pathology   MeSH
• Neoplasm Metastasis MeSH
• Adolescent MeSH
• Young Adult MeSH
• Biomarkers, Tumor genetics   metabolism   MeSH
• Bone Neoplasms diagnosis   genetics   metabolism   pathology   MeSH
• Follow-Up Studies MeSH
• Aged MeSH
• Transcription Factors metabolism   MeSH
• Matrix Attachment Region Binding Proteins metabolism   MeSH
• High-Throughput Nucleotide Sequencing MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Sarcosine is a widely discussed oncometabolite of prostate cells. Although several reports described connections between sarcosine and various phenotypic changes of prostate cancer (PCa) cells, there is still a lack of insights on the complex phenomena of its effects on gene expression patterns, particularly in non-malignant and non-metastatic cells. METHODS: To shed more light on this phenomenon, we performed parallel microarray profiling of RNA isolated from non-malignant (PNT1A), malignant (22Rv1), and metastatic (PC-3) prostate cell lines treated with sarcosine. Microarray results were experimentally verified using semi-quantitative-RT-PCR, clonogenic assay, through testing of the susceptibility of cells pre-incubated with sarcosine to anticancer agents with different modes of actions (inhibitors of topoisomerase II, DNA cross-linking agent, antimicrotubule agent and inhibitor of histone deacetylases) and by evaluation of activation of executioner caspases 3/7. RESULTS: We identified that irrespective of the cell type, sarcosine stimulates up-regulation of distinct sets of genes involved in cell cycle and mitosis, while down-regulates expression of genes driving apoptosis. Moreover, it was found that in all cell types, sarcosine had pronounced stimulatory effects on clonogenicity. Except of an inhibitor of histone deacetylase valproic acid, efficiency of all agents was significantly (P < 0.05) decreased in sarcosine pre-incubated cells. CONCLUSIONS: Our comparative study brings evidence that sarcosine affects not only metastatic PCa cells, but also their malignant and non-malignant counterparts and induces very similar changes in cells behavior, but via distinct cell-type specific targets.

• MeSH
• Apoptosis physiology   MeSH
• Humans MeSH
• Neoplasm Metastasis MeSH
• Biomarkers, Tumor metabolism   MeSH
• Neoplasm Proteins classification   metabolism   MeSH
• Prostatic Neoplasms * metabolism   pathology   MeSH
• Prostate * metabolism   pathology   MeSH
• Gene Expression Regulation, Neoplastic drug effects   MeSH
• Sarcosine metabolism   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH

Microfluidic devices are becoming mainstream tools to recapitulate in vitro the behavior of cells and tissues. In this study, we use microfluidic devices filled with hydrogels of mixed collagen-Matrigel composition to study the migration of lung cancer cells under different cancer invasion microenvironments. We present the design of the microfluidic device, characterize the hydrogels morphologically and mechanically and use quantitative image analysis to measure the migration of H1299 lung adenocarcinoma cancer cells in different experimental conditions. Our results show the plasticity of lung cancer cell migration, which turns from mesenchymal in collagen only matrices, to lobopodial in collagen-Matrigel matrices that approximate the interface between a disrupted basement membrane and the underlying connective tissue. Our quantification of migration speed confirms a biphasic role of Matrigel. At low concentration, Matrigel facilitates migration, most probably by providing a supportive and growth factor retaining environment. At high concentration, Matrigel slows down migration, possibly due excessive attachment. Finally, we show that antibody-based integrin blockade promotes a change in migration phenotype from mesenchymal or lobopodial to amoeboid and analyze the effect of this change in migration dynamics, in regards to the structure of the matrix. In summary, we describe and characterize a robust microfluidic platform and a set of software tools that can be used to study lung cancer cell migration under different microenvironments and experimental conditions. This platform could be used in future studies, thus benefitting from the advantages introduced by microfluidic devices: precise control of the environment, excellent optical properties, parallelization for high throughput studies and efficient use of therapeutic drugs.

• MeSH
• Spheroids, Cellular MeSH
• Diffusion MeSH
• Extracellular Matrix MeSH
• Phenotype MeSH
• Drug Combinations MeSH
• Hydrogels MeSH
• Collagen * chemistry   ultrastructure   MeSH
• Microscopy, Confocal MeSH
• Laminin * chemistry   ultrastructure   MeSH
• Humans MeSH
• Mechanical Phenomena MeSH
• Neoplasm Metastasis MeSH
• Microfluidics * methods   MeSH
• Cell Line, Tumor MeSH
• Tumor Cells, Cultured MeSH
• Tumor Microenvironment MeSH
• Cell Movement * MeSH
• Proteoglycans * chemistry   ultrastructure   MeSH
• Tissue Scaffolds * chemistry   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH