title: Acquisition of anoikis resistance up-regulates syndecan-4 expression in endothelial cells.
abstract: Anoikis is a programmed cell death induced upon cell detachment from extracellular matrix, behaving as a critical mechanism in preventing adherent-independent cell growth and attachment to an inappropriate matrix, thus avoiding colonization of distant organs. Cell adhesion plays an important role in neoplastic transformation. Tumors produce several molecules that facilitate their proliferation, invasion and maintenance, especially proteoglycans. The syndecan-4, a heparan sulfate proteoglycan, can act as a co-receptor of growth factors and proteins of the extracellular matrix by increasing the affinity of adhesion molecules to their specific receptors. It participates together with integrins in cell adhesion at focal contacts connecting the extracellular matrix to the cytoskeleton. Changes in the expression of syndecan-4 have been observed in tumor cells, indicating its involvement in cancer. This study investigates the role of syndecan-4 in the process of anoikis and cell transformation. Endothelial cells were submitted to sequential cycles of forced anchorage impediment and distinct lineages were obtained. Anoikis-resistant endothelial cells display morphological alterations, high rate of proliferation, poor adhesion to fibronectin, laminin and collagen IV and deregulation of the cell cycle, becoming less serum-dependent. Furthermore, anoikis-resistant cell lines display a high invasive potential and a low rate of apoptosis. This is accompanied by an increase in the levels of heparan sulfate and chondroitin sulfate as well as by changes in the expression of syndecan-4 and heparanase. These results indicate that syndecan-4 plays a important role in acquisition of anoikis resistance and that the conferral of anoikis resistance may suffice to transform endothelial cells.
authors.affiliation: Departamento de Ciências Biológicas, Universidade Federal de São Paulo, Diadema, SP, Brazil; Departamento de Bioquímica, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Bruna Ribeiro
authors.initials: BR
authors.lastname: Carneiro
authors.affiliation: Departamento de Ciências Biológicas, Universidade Federal de São Paulo, Diadema, SP, Brazil; Departamento de Bioquímica, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Paulo Castanho A
authors.initials: PC
authors.lastname: Pernambuco Filho
authors.affiliation: Departamento de Ciências Biológicas, Universidade Federal de São Paulo, Diadema, SP, Brazil; Departamento de Bioquímica, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Ana Paula de Sousa
authors.initials: AP
authors.lastname: Mesquita
authors.affiliation: Departamento de Ciências Biológicas, Universidade Federal de São Paulo, Diadema, SP, Brazil; Departamento de Bioquímica, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Douglas Santos
authors.initials: DS
authors.lastname: da Silva
authors.affiliation: Departamento de Bioquímica, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Maria Aparecida S
authors.initials: MA
authors.lastname: Pinhal
authors.affiliation: Departamento de Bioquímica, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Helena B
authors.initials: HB
authors.lastname: Nader
authors.affiliation: Departamento de Ciências Biológicas, Universidade Federal de São Paulo, Diadema, SP, Brazil; Departamento de Bioquímica, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Carla Cristina
authors.initials: CC
authors.lastname: Lopes
mesh_terms: D000818:Animals; D023102:Anoikis; D001011:Aorta / Q000166:cytology*; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002448:Cell Adhesion; D002453:Cell Cycle; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D053671:Syndecan-4 / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation; D000099175:Heparanase
chemical_list: D001973:Bromodeoxyuridine; D005966:Glucuronidase; D053671:Syndecan-4; D000099175:Heparanase