Premium
Extracellular matrix inhibits apoptosis and enhances endothelial cell differentiation by a NFκB‐dependent mechanism
Author(s) -
Wang Wengong,
Passaniti Antonino
Publication year - 1999
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19990601)73:3<321::aid-jcb4>3.0.co;2-0
Subject(s) - extracellular matrix , apoptosis , etoposide , microbiology and biotechnology , cancer research , nf κb , cell growth , biology , chemistry , medicine , signal transduction , biochemistry , chemotherapy
Hormonal and environmental factors that control the growth, differentiation, and regression of the vasculature are of fundamental importance in tumorigenesis and in the choice of therapeutic strategies. To test the hypothesis that estradiol (E 2 ) and basement membrane proteins would affect the survival of vascular endothelial cells (EC), immortalized human umbilical vein endothelial cells (ECV304) were examined for their response to the chemotherapeutic drugs taxol and etoposide. ECV cell apoptosis was inhibited by E 2 (taxol only) or attachment to extracellular matrix (ECM) (taxol or etoposide). E 2 increased ECV growth, while ECM binding resulted in growth arrest and differentiation. Apoptosis was associated with decreased levels of Bcl‐2 and p21 proteins. E 2 prevented down‐regulation of p21 and Bcl‐2 induced by taxol but did not prevent the down‐regulation of p21 induced by etoposide, consistent with the failure of E 2 to inhibit etoposide‐induced cell death. However, ECM prevented p21 and Bcl‐2 down‐regulation induced by taxol or etoposide. Persistent activation of NFκB occurred after attachment of ECV cells to ECM, suggesting a role in survival or differentiation. IκBα levels were not affected by taxol but were reduced by etoposide treatment, while IκBβ levels did not change with drug treatment. E 2 did not alter the levels of IκBα or IκBβ. Interestingly, levels of IκBα and IκBβ declined in etoposide‐treated ECV cells on ECM concomitant with the elevation of NFκB, suggesting that in these cells degradation of IκB may be responsible for NFκB activation. In agreement with these data, anti‐sense NFκB treatment of ECV cells inhibited differentiation on ECM, but did not affect cell survival. In conclusion, culture of ECV cells on ECM or treatment with E 2 inhibited apoptosis. NFκB activation by ECM was necessary for cellular differentiation, rather than inhibition, of apoptosis. J. Cell. Biochem. 73:321–331, 1999. © 1999 Wiley‐Liss, Inc.