Browsing by Author "Díaz, Jorge"
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Item Caveolin-1-containing extracellular vesicles transport adhesion proteins and promote malignancy in breast cancer cell lines(Future Medicine Ltd, 2018) Campos, America; Salomon, Carlos; Bustos, Rocío; Díaz, Jorge; Martínez, Samuel; Silva, Verónica; Reyes, Constanza; Díaz-Valdivia, Natalia; Varas-Godoy, Manuel; Lobos-González, Lorena; Quest, AndrewBreast cancer is one of the most frequently diagnosed cancers and the leading cause of cancer-related deaths in women worldwide, whereby mortality is largely attributable to the development of distant metastasis. Caveolin-1 (CAV1) is a multifunctional membrane protein that is typically upregulated in the final stages of cancer and promotes migration and invasion of tumor cells. Elevated levels of CAV1 have been detected in extracellular vesicles (EVs) from advanced cancer patients. EVs are lipid enclosed vesicular structures that contain bioactive proteins, DNA and RNAs, which can be transferred to other cells and promote metastasis. Therefore, we hypothesized that CAV1 containing EVs released from breast cancer cells may enhance migration and invasion of recipient cells. EVs were purified from conditioned media of MDA-MB-231 wild-type (WT), MDA-MB-231 (shCAV1; possessing the plasmid pLKO.1 encoding a 'small hairpin' directed against CAV1) and MDA-MB-231 (shC) short hairpin control cells. Nanoparticle tracking analysis revealed an average particle size of 40-350 nm for all preparations. As anticipated, CAV1 was detected in MDA-MB-231 WT and shC EVs, but not in MDA-MB-231 (shCAV1) EVs. Mass spectrometry analysis revealed the presence of specific cell adhesion-related proteins, such as Cyr61, tenascin (TNC) and S100A9 only in WT and shC, but not in shCAV1 EVs. Importantly, EVs containing CAV1 promoted migration and invasion of cells lacking CAV1. We conclude that the presence of CAV1 in EVs from metastatic breast cancer cells is associated with enhanced migration and invasiveness of recipient cells in vitro, suggesting that intercellular communication promoted by EVs containing CAV1 will likely favor metastasis in vivo.Item Enfermedad quística adventicial de la arteria poplítea. Presentación imagenológica de una causa rara de claudicación intermitente(2019) Cacho, Javier; Olivares, Juan; Díaz, Jorge; Faure, María; Pires, YumayAdventitial cystic disease of the popliteal artery is a rare condition of uncertain etiology, which presents as intermittent claudication of the lower extremity in middle-age patients. We report a 44-year-old man presenting with intermittent claudication of his left leg. MR angiography showed cystic parietal lesions that caused compression with partial occlusion of the left popliteal artery. Surgical resection of the affected segment was performed, with venous graft interposition. The histopathological analysis of the surgical specimen was consistent with cystic adventitial disease.Item Protocolo abreviado de resonancia magnética en espondiloartritis: más allá de la sacroileítis(Sociedad Médica de Santiago, 2015) Schiappacasse, Giancarlo; Díaz, Jorge; Alvayay, PabloSpondyloarthritis is a group of diseases that seriously hampers quality of life. Diagnostic criteria, in which images play an important role, have evolved over time. The most recent diagnostic criteria, published in 2009, included magnetic resonance imaging (MRI) of the sacroiliac joints for the first time. This technique achieves an early diagnosis and provides a useful tool for the evaluation and prediction of response to biological therapy. Herein, we describe the different MRI findings in spondyloarthropathies. We also highlight the use of a protocol that includes the sacroiliac joints and spine and that does not consider the routine use of paramagnetic contrast.Item Src-family kinase inhibitors block early steps of caveolin-1-enhanced lungmetastasis by melanoma cells(2020) Ortiz, Rina; Díaz, Jorge; Díaz-Valdivia, Natalia; Martínez, Samuel; Simón, Layla; Contreras, Pamela; Lobos-González, Lorena; Guerrero, Simón; Leyton, Lisette; Quest, Andrew F.G.In advanced stages of cancer disease, caveolin-1 (CAV1) expression increases and correlates with increased migratory and invasive capacity of the respective tumor cells. Previous findings from our laboratory revealed that specific ECM-integrin interactions and tyrosine-14 phosphorylation of CAV1 are required for CAV1-enhanced melanoma cell migration, invasion and metastasis in vivo. In this context, CAV1 phosphorylation on tyrosine-14 mediated by non-receptor Src-family tyrosine kinases seems to be important; however, the effect of Src-family kinase inhibitors on CAV1-enhanced metastasis in vivo has not been studied. Here, we evaluated the effect of CAV1 and c-Abl overexpression, as well as the use of the Src-family kinase inhibitors, PP2 and dasatinib (more specific for Src/Abl) in lung metastasis of B16F10 melanoma cells. Overexpression of CAV1 and c-Abl enhanced CAV1 phosphorylation and the metastatic potential of the B16F10 murine melanoma cells. Alternatively, treatment with PP2 or dasatinib for 2 h reduced CAV1 tyrosine-14 phosphorylation and levels recovered fully within 12 h of removing the inhibitors. Nonetheless, pre-treatment of cells with these inhibitors for 2 h sufficed to prevent migration, invasion and trans-endothelial migration in vitro. Importantly, the transient decrease in CAV1 phosphorylation by these kinase inhibitors prevented early steps of CAV1-enhanced lung metastasis by B16F10 melanoma cells injected into the tail vein of mice. In conclusion, this study underscores the relevance of CAV1 tyrosine-14 phosphorylation by Src-family kinases during the first steps of the metastatic sequence promoted by CAV1. These findings open up potential options for treatment of metastatic tumors in patients in which Src-family kinase activation and CAV1 overexpression favor dissemination of cancer cells to secondary sites.