Histology and histopathology Vol.28, nº11 (2013)
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- PublicationOpen AccessSPARC is up-regulated during skeletal muscle regeneration and inhibits myoblast differentiation(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2013) Petersson, Stine Juhl; Jørgensen, Louise Helskov; Andersen, Ditte C.; Nørgaard, Rikke C.; Jensen3, Charlotte Harken; Schrøder, Henrik DaaSkeletal muscle repair is mediated primarily by the muscle stem cell, the satellite cell. Several factors, including extracellular matrix, are known to regulate satellite cell function and regeneration. One factor, the matricellular Secreted Protein Acidic and Rich in Cysteine (SPARC) is highly up-regulated during skeletal muscle disease, but its function remains elusive. In the present study, we demonstrate a prominent yet transient increase in SPARC mRNA and protein content during skeletal muscle regeneration that correlates with the expression profile of specific muscle factors like MyoD, Myf5, Myf6, Myogenin, NCAM, CD34, and M-Cadherin, all known to be implicated in satellite cell activation/proliferation following muscle damage. This up regulation was detected in more cell types. Ectopic expression of SPARC in the muscle progenitor cell line C2C12 was performed to mimic the high levels of SPARC seen in muscle disease. SPARC overexpression almost completely abolished myogenic differentiation in these cultures as determined by substantially reduced levels of myogenic factors (Pax7, Myf5, Myod, Mef2a, Myogenin, and Myostatin) and a lack of multinucleated myotubes. These results demonstrate that there is a delicate temporal regulation of SPARC to which more sources in the micro environment contribute, and that disturbances in this, such as extensive up regulation, may have an adverse effect on muscle regeneration.
- PublicationOpen AccessClinicopathologic characteristics of STAT1 positive/interleukin-8 negative subgroup in triple negative breast cancer defined by surrogate immunohistochemistry(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2013) Kim, Sewha; Kim, Do Hee; Jung, Woo-Hee; Koo, Ja SeungBackground: The aim of this study was to define immune-related triple negative breast cancer (TNBC) using immunohistochemistry for STAT1, CD20, CD3, IL-8, and IFN-γ and to assess its clinicopathologic characteristics. Material and methods: Tissues from 133 cases of TNBC were used for a tissue microarray. Expression of STAT1, CD20, CD3, IL-8, and IFN-γ were evaluated by immunohistochemical staining of the tissue microarrays. Immune-related type was defined as TNBC which was positive for STAT1 and negative for IL-8. A separate assessment of IL-8 and STAT1 status in tumor and stroma compartment was used to further classify immune-related type into tumor-based and stroma-based immune-related TNBC. Results: Stroma-based, immune-related TNBC showed a significantly smaller central acellular zone (p=0.043), more lymphocytic infiltration (p<0.001), higher CD20 index (p=0.001), and higher CD3 index (p=0.018) than stroma-based, non-immune-related TNBC. IL-8 was independently associated with shorter disease-free survival (Hazard ratio: 3.804, 95% CI: 1.234-11.729, p=0.020) and shorter overall survival (Hazard ratio: 3.434, 95% CI: 1.132-10.414, p=0.029). Conclusions: Immune-related proteins such as STAT1, IFN-γ, IL-8, and CD20 were variably expressed in TNBCs. Stroma-based, immune-related TNBC (when positive for stromal STAT1 and negative for stromal IL-8) showed significantly higher lymphocytic infiltration including both CD3 positive T cell and CD20 positive B cell.
- PublicationOpen AccessSignaling molecules and pathways involved in MSC tumor tropism(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2013) Ho, Ivy AW; Lam, Paula YPHuman bone marrow is a reservoir containing cells with different self-renewal capabilities, such as mesenchymal stem cells (MSC) and hematopoeitic stem cells (HSC). MSC in particular have been increasingly used in preclinical and clinical treatment of tissue regenerative disorder. Understanding the molecular mechanisms underlying MSC homing and mobilization is critical to the design of rational cell therapy approaches. In this review, we will discuss the key molecular mechanisms that govern the homing of MSC to bone marrow, the mobilization of MSC to tumors and injured sites via circulation, and strategies that enhance MSC migration.
- PublicationOpen AccessSimultaneous phenotypic and genetic characterization of single circulating tumor cells from colon cancer patients(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2013) Campos, María; Luque, Rafael; Jiménez, Juan; Martínez, Rafael; Warleta, Fernando; Sánchez-Quesada, Cristina; Delgado-Rodríguez, Miguel; Calvo, Alfonso; Gaforio, José J.Since circulating tumor cells (CTCs) have metastatic potential, their genetic and phenotypic characteristics could provide crucial information to establish the most effective therapy. We assessed the clinical utility of a methodology that allows the simultaneous analysis of CTC phenotype and genotype in colon cancer patients and, in addition, whether this methodology could provide complementary information to that obtained by the primary tumor biopsy. Thirty-three non-metastatic (stages 0-III) colon cancer patients and 9 healthy donor samples were evaluated. All peripheral blood samples (10 ml) were analyzed by cytokeratin immunomagnetic enrichment. Eight samples were analyzed by immunocytochemistry and 25 samples were analyzed by FICTION technique for simultaneous cytokeratin expression and chromosome 17 and ERBB2 gene status. A further study was carried out in one patient who showed CTC heterogeneity in chromosomal abnormalities. We analyzed HER2 protein expression on CTCs and FISH and HER2 protein expression in primary tumor of this patient. Our results show that 9.09% of patients had cytokeratin-positive CTCs (CK+/CTCs in peripheral blood). One of the patients showed heterogeneity in chromosomal 17 abnormalities and two different CK expression patterns on CTCs: one CK+/CTCs and one CK-/CTCs. Furthermore, 63.33% of these CTCs overexpressed HER2 protein while the primary tumor of this patient was diploid and did not express HER2 protein. We describe a methodology that allows the simultaneous genetic and phenotypic analysis of CTCs in colon cancer patients, which may provide essential information to select patients who might benefit from specific therapy.
- PublicationOpen AccessRole of PRDM16 in the activation of brown fat programming. Relevance to the development of obesity(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2013) Becerril, Sara; Gómez-Ambrosi, Javier; Martín, Marina; Moncada, Rafael; Sesma, Pilar; Burrell, María A.; Frühbeck, GemaFrom a histological and functional point of view, two types of adipose tissue can be identified. As opposed to the mainly unilocular white adipocytes, brown adipocytes possess plenty of small multilocular lipid droplets and dissipate energy as heat. Moreover, two distinct types of brown adipose cells exist. In vivo fate mapping experiments of brown adipose tissue (BAT) precursors suggest that classical brown adipocytes and skeletal myoblasts originate from a common mesenchymal, myogenic factor 5 (Myf5)-positive precursor cell. In addition to the classical brown adipocytes, thermogenic brown-like adipocytes (brite/beige cells) may appear within white adipose tissue (WAT) depots, sharing many of the morphological and functional features of brown adipocytes, but arising from a Myf5-negative lineage. In humans, the conversion of white fat cells into brite adipocytes could be a strategy to increase energy expenditure. The zinc finger transcription factor Prdm16 controls the bidirectional fate decision between brown adipocytes and myoblasts. Prdm16 determines the brown fat-like programme and thermogenesis in both brown and white adipose tissues. Moreover, the expression of this transcriptional regulator is strongly correlated with beige cell-selective genes. From a therapeutical point of view, the potential of inducing BAT or the transdifferentiation of WAT into beige cells by enhancing Prdm16 expression, as well as the identification of mechanisms of Prdm16 function and regulation represent potentially exciting new approaches for treatment or prevention of obesity and related diseases.
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