Biomedical Research Consortium of Chile

Santiago, Chile

Biomedical Research Consortium of Chile

Santiago, Chile
SEARCH FILTERS
Time filter
Source Type

Erices R.,University of Santiago de Chile | Cubillos S.,University of Santiago de Chile | Aravena R.,University of Santiago de Chile | Aravena R.,Santo Tomás University of Chile | And 31 more authors.
Oncotarget | Year: 2017

Clinical studies have suggested a survival benefit in ovarian cancer patients with type 2 diabetes mellitus taking metformin, however the mechanism by which diabetic concentrations of metformin could deliver this effect is still poorly understood. Platelets not only represent an important reservoir of growth factors and angiogenic regulators, they are also known to participate in the tumor microenvironment implicated in tumor growth and dissemination. Herein, we investigated if diabetic concentrations of metformin could impinge upon the previously reported observation that platelet induces an increase in the tube forming capacity of endothelial cells (angiogenesis) and upon ovarian cancer cell aggressiveness. We demonstrate that metformin inhibits the increase in angiogenesis brought about by platelets in a mechanism that did not alter endothelial cell migration. In ovarian cancer cell lines and primary cultured cancer cells isolated from the ascitic fluid of ovarian cancer patients, we assessed the effect of combinations of platelets and metformin upon angiogenesis, migration, invasion and cancer sphere formation. The enhancement of each of these parameters by platelets was abrogated by the present of metformin in the vast majority of cancer cell cultures tested. Neither metformin nor platelets altered proliferation; however, metformin inhibited the increase in phosphorylation of focal adhesion kinase induced by platelets. We present the first evidence suggesting that concentrations of metformin present in diabetic patients may reduce the actions of platelets upon both endothelial cells and cancer cell survival and dissemination.


Racordon D.,University of Santiago de Chile | Valdivia A.,University of Santiago de Chile | Mingo G.,University of Santiago de Chile | Erices R.,University of Santiago de Chile | And 26 more authors.
Scientific Reports | Year: 2017

Vasculogenic mimicry (VM) describes a process by which cancer cells establish an alternative perfusion pathway in an endothelial cell-free manner. Despite its strong correlation with reduced patient survival, controversy still surrounds the existence of an in vitro model of VM. Furthermore, many studies that claim to demonstrate VM fail to provide solid evidence of true hollow channels, raising concerns as to whether actual VM is actually being examined. Herein, we provide a standardized in vitro assay that recreates the formation of functional hollow channels using ovarian cancer cell lines, cancer spheres and primary cultures derived from ovarian cancer ascites. X-ray microtomography 3D-reconstruction, fluorescence confocal microscopy and dye microinjection conclusively confirm the existence of functional glycoprotein-rich lined tubular structures in vitro and demonstrate that many of structures reported in the literature may not represent VM. This assay may be useful to design and test future VM-blocking anticancer therapies. © 2017 The Author(s).


Orellana R.,University of Santiago de Chile | Orellana R.,Biomedical Research Consortium of Chile | Kato S.,University of Santiago de Chile | Kato S.,Biomedical Research Consortium of Chile | And 30 more authors.
BMC Cancer | Year: 2015

Background: An increase in circulating platelets, or thrombocytosis, is recognized as an independent risk factor of bad prognosis and metastasis in patients with ovarian cancer; however the complex role of platelets in tumor progression has not been fully elucidated. Platelet activation has been associated with an epithelial to mesenchymal transition (EMT), while Tissue Factor (TF) protein expression by cancer cells has been shown to correlate with hypercoagulable state and metastasis. The aim of this work was to determine the effect of platelet-cancer cell interaction on TF and "Metastasis Initiating Cell (MIC)" marker levels and migration in ovarian cancer cell lines and cancer cells isolated from the ascetic fluid of ovarian cancer patients. Methods: With informed patient consent, ascitic fluid isolated ovarian cancer cells, cell lines and ovarian cancer spheres were co-cultivated with human platelets. TF, EMT and stem cell marker levels were determined by Western blotting, flow cytometry and RT-PCR. Cancer cell migration was determined by Boyden chambers and the scratch assay. Results: The co-culture of patient-derived ovarian cancer cells with platelets causes: 1) a phenotypic change in cancer cells, 2) chemoattraction and cancer cell migration, 3) induced MIC markers (EMT/stemness), 3) increased sphere formation and 4) increased TF protein levels and activity. Conclusions: We present the first evidence that platelets act as chemoattractants to cancer cells. Furthermore, platelets promote the formation of ovarian cancer spheres that express MIC markers and the metastatic protein TF. Our results suggest that platelet-cancer cell interaction plays a role in the formation of metastatic foci. © 2015 Orellana et al.; licensee BioMed Central.


Pinto M.P.,University of Santiago de Chile | Sotomayor P.,Andrés Bello University | Carrasco-Avino G.,University of Chile | Corvalan A.H.,University of Santiago de Chile | And 4 more authors.
International Journal of Molecular Sciences | Year: 2016

Tumor angiogenesis is widely recognized as one of the "hallmarks of cancer". Consequently, during the last decades the development and testing of commercial angiogenic inhibitors has been a central focus for both basic and clinical cancer research. While antiangiogenic drugs are now incorporated into standard clinical practice, as with all cancer therapies, tumors can eventually become resistant by employing a variety of strategies to receive nutrients and oxygen in the event of therapeutic assault. Herein, we concentrate and review in detail three of the principal mechanisms of antiangiogenic therapy escape: (1) upregulation of compensatory/alternative pathways for angiogenesis; (2) vasculogenic mimicry; and (3) vessel co-option. We suggest that an understanding of how a cancer cell adapts to antiangiogenic therapy may also parallel the mechanisms employed in the bourgeoning tumor and isolated metastatic cells delivering responsible for residual disease. Finally, we speculate on strategies to adapt antiangiogenic therapy for future clinical uses. © 2016 by the authors; licensee MDPI, Basel, Switzerland.


Villavicencio A.,University of Chile | Aguilar G.,University of Michigan | Acua J.,University of Chile | Gabler F.,University of Chile | And 6 more authors.
International Journal of Obesity | Year: 2012

Enhanced endometrial proliferation correlates obesity to type-I (estrogen-dependent) endometrial cancer (EC). Our aim was to distinguish obese women (without EC) with differing endometrial proliferation. Endometrial and blood samples were obtained from normal-weight and obese women without EC. Type-I EC samples were obtained from obese patients. On measuring endometrial proliferation (Ki67 and phosphorylated histone H3 (p-H3)), two groups of obese women without EC were identified: obeseHigh Proliferating (O HP) and obeseLow Proliferating (OLP). Increased Ki67 (88.5%, P<0.001), p-H3 (62.6%, P<0.01), 17Β-estradiol/ progesterone ratio (46.3%, P<0.01) and endometrial estrogen receptor alpha (ERα) (82.2%, P<0.001) were observed in OHP compared with OLP patients. ECs possessed similar ERα and enhanced proliferation as OHP, suggesting that OHP women are at higher risk of type-I EC. OLP women were indistinguishable from normal-weight women regarding these determinants of endometrial proliferation, ERα and 17Β-estradiol/progesterone ratio. Our data may further define the obesity phenotype in regards to type-I EC risk and may help identify obese women more susceptible to develop type-I EC, allowing early intervention and a potential reduction in mortality. © 2012 Macmillan Publishers Limited All rights reserved.

Loading Biomedical Research Consortium of Chile collaborators
Loading Biomedical Research Consortium of Chile collaborators