Browsing by Author "Lange, Soledad"
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- ItemAntiangiogenic, antimigratory and antiinflammatory effects of 2-methoxyestradiol in zebrafish larvae(2013) Quezada, Marisol; Alvarez, Marjorie; Peña, Oscar A.; Henríquez, Soledad; D' Alencon, Claudia A.; Lange, Soledad; Oliva, Barbara; Owen, Gareth Ivor; Allende, Miguel L.
- ItemCharacterization and phenotypic variation with passage number of cultured human endometrial adenocarcinoma cells(2008) Kato Cardemil, Sumie Rode; Villalón, Manuel J.; Cuello F., Mauricio; Owen, Gareth Ivor; Espinoza, Natalia; Lange, Soledad
- ItemCoagulation Factor Xa Promotes Solid Tumor Growth, Experimental Metastasis and Endothelial Cell Activation.(2019) Arce, Maximiliano; Pinto, Mauricio P.; Galleguillos, Macarena; Muñoz, Catalina; Lange, Soledad; Ramirez, Carolina; Erices, Rafaela; Gonzalez, Pamela; Velasquez, Ethel; Tempio, Fabián; Lopez, Mercedes N.; Salazar-Onfray, Flavio; Cautivo, Kelly; Kalergis, Alexis M.; Cruz, Sebastián; Lladser, Álvaro; Lobos-González, Lorena; Valenzuela, Guillermo; Olivares, Nixa; Sáez, Claudia; Koning, Tania; Sánchez, Fabiola A.; Fuenzalida, Patricia; Godoy, Alejandro; Contreras Orellana, Pamela; Leyton, Lisette; Lugano, Roberta; Dimberg, Anna; Quest, Andrew F.G.; Owen, Gareth I.Hypercoagulable state is linked to cancer progression; however, the precise role of the coagulation cascade is poorly described. Herein, we examined the contribution of a hypercoagulative state through the administration of intravenous Coagulation Factor Xa (FXa), on the growth of solid human tumors and the experimental metastasis of the B16F10 melanoma in mouse models. FXa increased solid tumor volume and lung, liver, kidney and lymph node metastasis of tail-vein injected B16F10 cells. Concentrating on the metastasis model, upon coadministration of the anticoagulant Dalteparin, lung metastasis was significantly reduced, and no metastasis was observed in other organs. FXa did not directly alter proliferation, migration or invasion of cancer cells in vitro. Alternatively, FXa upon endothelial cells promoted cytoskeleton contraction, disrupted membrane VE-Cadherin pattern, heightened endothelial-hyperpermeability, increased inflammatory adhesion molecules and enhanced B16F10 adhesion under flow conditions. Microarray analysis of endothelial cells treated with FXa demonstrated elevated expression of inflammatory transcripts. Accordingly, FXa treatment increased immune cell infiltration in mouse lungs, an effect reduced by dalteparin. Taken together, our results suggest that FXa increases B16F10 metastasis via endothelial cell activation and enhanced cancer cell-endothelium adhesion advocating that the coagulation system is not merely a bystander in the process of cancer metastasis.
- ItemProgesterone promotes focal adhesion formation and migration in breast cancer cells through induction of protease-activated receptor-1(BIOSCIENTIFICA LTD, 2012) Diaz, Jorge; Aranda, Evelyn; Henriquez, Soledad; Quezada, Marisol; Espinoza, Estefania; Loreto Bravo, Maria; Oliva, Barbara; Lange, Soledad; Villalon, Manuel; Jones, Marius; Brosens, Jan J.; Kato, Sumie; Cuello, Mauricio A.; Knutson, Todd P.; Lange, Carol A.; Leyton, Lisette; Owen, Gareth I.Progesterone and progestins have been demonstrated to enhance breast cancer cell migration, although the mechanisms are still not fully understood. The protease-activated receptors (PARs) are a family of membrane receptors that are activated by serine proteases in the blood coagulation cascade. PAR1 (F2R) has been reported to be involved in cancer cell migration and overexpressed in breast cancer. We herein demonstrate that PAR1 mRNA and protein are upregulated by progesterone treatment of the breast cancer cell lines ZR-75 and T47D. This regulation is dependent on the progesterone receptor (PR) but does not require PR phosphorylation at serine 294 or the PR proline-rich region mPRO. The increase in PAR1 mRNA was transient, being present at 3 h and returning to basal levels at 18 h. The addition of a PAR1-activating peptide (aPAR1) to cells treated with progesterone resulted in an increase in focal adhesion (FA) formation as measured by the cellular levels of phosphorylated FA kinase. The combined but not individual treatment of progesterone and aPAR1 also markedly increased stress fiber formation and the migratory capacity of breast cancer cells. In agreement with in vitro findings, data mining from the Oncomine platform revealed that PAR1 expression was significantly upregulated in PR-positive breast tumors. Our observation that PAR1 expression and signal transduction are modulated by progesterone provides new insight into how the progestin component in hormone therapies increases the risk of breast cancer in postmenopausal women. Journal of Endocrinology (2012) 214, 165-175
- ItemThe oestrogen metabolite 2-methoxyoestradiol alone or in combination with tumour necrosis factor-related apoptosis-inducing ligand mediates apoptosis in cancerous but not healthy cells of the human endometrium(BIOSCIENTIFICA LTD, 2007) Kato, Sumie; Sadarangani, Anil; Lange, Soledad; Villalon, Manuel; Branes, Jorge; Brosens, Jan J.; Owen, Gareth I.; Cuello, MauricioCancers of the reproductive tract account for 12% of all malignancies in women. As previous studies have shown that oestrogen metabolites can cause apoptosis, we characterised the effect of oestrogen and oestrogen metabolites on non-cancerous and cancerous human endometrial cells. Herein, we demonstrate that 2-methoxyoestradiol (2ME), but not 17 beta-oestradiol, induces apoptosis in cancer cell lines and primary cultured tumours; of endometrial origin. In contrast, 2ME had no effect on cell viability of corresponding normal tissue. This ability of 2ME to induce apoptosis does not require oestrogen receptor activation, but is associated with increased entry into the G2/M phases of the cell cycle and the activation of both the intrinsic and the extrinsic apoptotic pathways. The selective behaviour of 2ME on cancerous as opposed to normal tissue may be due to a reduction in 17 beta -hydroxysteroid dehydrogenase type 11 levels in cancer cells and to a differential down-regulation of superoxide dismutase. Furthermore, we demonstrate that pre-treatment with 2ME enhances the sensitivity of reproductive tract cancer cells to the apoptotic drug tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), without the loss in cell viability to normal cells incurred by currently chemotherapeutic drugs. In conclusion, 2ME, alone or in combination with TRAIL, may be an effective treatment for cancers of uterine origin with minimal toxicity to corresponding healthy female reproductive tissue.
- ItemTRAIL mediates apoptosis in cancerous but not normal primary cultured cells of the human reproductive tract (vol 12, pg 73, 2007)(SPRINGER, 2007) Sadarangani, Anil; Kato, Sumie; Espinoza, Natalia; Lange, Soledad; Llados, Carmen; Espinosa, Marisol; Villalon, Manuel; Lipkowitz, Stanley; Cuello, Mauricio; Owen, Gareth I.