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Three-dimensional growth as multicellular spheroid activates the proangiogenic phenotype of colorectal carcinoma cells via LFA-1-dependent VEGF: implications on hepatic micrometastasis
dc.contributor.author | Valcarcel, María | |
dc.contributor.author | Arteta Ruiz, Beatriz | |
dc.contributor.author | Jaureguibeitia, Arrate | |
dc.contributor.author | Lopategi Martínez, Aritz | |
dc.contributor.author | Martínez, Iñigo | |
dc.contributor.author | Mendoza, Lorea | |
dc.contributor.author | Muruzabal, Francisco J. | |
dc.contributor.author | Salado, Clarisa | |
dc.contributor.author | Vidal Vanaclocha, Fernando | |
dc.date.accessioned | 2014-04-01T17:16:44Z | |
dc.date.available | 2014-04-01T17:16:44Z | |
dc.date.issued | 2008-10 | |
dc.identifier.citation | Journal of Translational Medicine 6 : (2008) // Article n. 57 | es |
dc.identifier.issn | 1479-5876 | |
dc.identifier.uri | http://hdl.handle.net/10810/11908 | |
dc.description.abstract | Background: The recruitment of vascular stromal and endothelial cells is an early event occurring during cancer cell growth at premetastatic niches, but how the microenvironment created by the initial three-dimensional (3D) growth of cancer cells affects their angiogenesis-stimulating potential is unclear. Methods: The proangiogenic profile of CT26 murine colorectal carcinoma cells was studied in seven-day cultured 3D-spheroids of <300 mu m in diameter, produced by the hanging-drop method to mimic the microenvironment of avascular micrometastases prior to hypoxia occurrence. Results: Spheroid-derived CT26 cells increased vascular endothelial growth factor (VEGF) secretion by 70%, which in turn increased the in vitro migration of primary cultured hepatic sinusoidal endothelium (HSE) cells by 2-fold. More importantly, spheroid-derived CT26 cells increased lymphocyte function associated antigen (LFA)-1-expressing cell fraction by 3-fold; and soluble intercellular adhesion molecule (ICAM)-1, given to spheroid-cultured CT26 cells, further increased VEGF secretion by 90%, via cyclooxygenase (COX)-2-dependent mechanism. Consistent with these findings, CT26 cancer cells significantly increased LFA-1 expression in non-hypoxic avascular micrometastases at their earliest inception within hepatic lobules in vivo; and angiogenesis also markedly increased in both subcutaneous tumors and hepatic metastases produced by spheroid-derived CT26 cells. Conclusion: 3D-growth per se enriched the proangiogenic phenotype of cancer cells growing as multicellular spheroids or as subclinical hepatic micrometastases. The contribution of integrin LFA-1 to VEGF secretion via COX-2 was a micro environmental-related mechanism leading to the pro-angiogenic activation of soluble ICAM-1-activated colorectal carcinoma cells. This mechanism may represent a new target for specific therapeutic strategies designed to block colorectal cancer cell growth at a subclinical micrometastatic stage within the liver. | es |
dc.description.sponsorship | Supported in part by Pharmakine S. L., and by grants from the CICYT of the Spanish government (SAF2006-09341), and the Basque Country Government (IT-487-07) | es |
dc.language.iso | eng | es |
dc.publisher | BioMed Central | es |
dc.rights | info:eu-repo/semantics/openAccess | es |
dc.subject | intercellular-adhesion molecule-1 | es |
dc.subject | sinusoidal endothelial cells | es |
dc.subject | cancer cells | es |
dc.subject | in-vivo | es |
dc.subject | tumor spheroids | es |
dc.subject | soluble icam-1 | es |
dc.subject | stellate cells | es |
dc.subject | rat liver | es |
dc.subject | expression | es |
dc.subject | metastasis | es |
dc.title | Three-dimensional growth as multicellular spheroid activates the proangiogenic phenotype of colorectal carcinoma cells via LFA-1-dependent VEGF: implications on hepatic micrometastasis | es |
dc.type | info:eu-repo/semantics/article | es |
dc.rights.holder | © 2008 Valcárcel et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. | es |
dc.relation.publisherversion | http://www.translational-medicine.com/content/6/1/57 | es |
dc.identifier.doi | 10.1186/1479-5876-6-57 | |
dc.departamentoes | Biología celular e histología | es_ES |
dc.departamentoeu | Zelulen biologia eta histologia | es_ES |
dc.subject.categoria | BIOCHEMISTRY AND MOLECULAR BIOLOGY | |
dc.subject.categoria | MEDICINE |