The Novel SPARC Family Member SMOC-2 Potentiates Angiogenic Growth Factor Activity

SMOC-2 is a novel member of the SPARC family of matricellular proteins. The purpose of this study was to determine whether SMOC-2 can modulate angiogenic growth factor activity and angiogenesis. SMOC-2 was localized in the extracellular periphery of cultured human umbilical vein endothelial cells (HUVECs). Ectopically expressed SMOC-2 was also secreted into the tissue culture medium. In microarray profiling experiments, a recombinant SMOC-2 adenovirus induced the expression of transcripts required for cell cycle progression in HUVECs. Consistent a for in a SMOC-2 also endothelial growth factor growth factor to Ectopically expressed SMOC-2 of in the of SMOC-2 in this SMOC-2 and The angiogenic activity of SMOC-2 was also in of SMOC-2 SMOC-2 adenovirus induced a in the of cells a growth factor and SMOC-2 a cell SMOC-2 is a novel angiogenic factor angiogenic of growth SMOC-2 is a novel member of the SPARC family of matricellular proteins. The purpose of this study was to determine whether SMOC-2 can modulate angiogenic growth factor activity and angiogenesis. SMOC-2 was localized in the extracellular periphery of cultured human umbilical vein endothelial cells (HUVECs). Ectopically expressed SMOC-2 was also secreted into the tissue culture medium. In microarray profiling experiments, a recombinant SMOC-2 adenovirus induced the expression of transcripts required for cell cycle progression in HUVECs. Consistent a for in a SMOC-2 also endothelial growth factor growth factor to Ectopically expressed SMOC-2 of in the of SMOC-2 in this SMOC-2 and The angiogenic activity of SMOC-2 was also in of SMOC-2 SMOC-2 adenovirus induced a in the of cells a growth factor and SMOC-2 a cell SMOC-2 is a novel angiogenic factor angiogenic of growth the of is a in and in the of the to in the of this growth and extracellular the matricellular in in and angiogenesis. extracellular to the extracellular cells and the extracellular matricellular the and the SPARC secreted and in growth endothelial growth growth secreted SMOC-2 and to of human endothelial cell growth human umbilical vein endothelial endothelial secreted and in growth endothelial growth growth secreted SMOC-2 and to of human endothelial cell growth human umbilical vein endothelial endothelial and in family of proteins. expressed in cell and expressed and is tissue is expressed and expression in is expressed in and tissue and for SPARC to a and in In the of SPARC cell to cell to the extracellular and cell SPARC cell cycle progression and to and extracellular and a in the of SPARC to growth and growth factor and endothelial growth factor SPARC the of growth factor and growth factor is SPARC is for angiogenesis. is the in is cell into is also the of SPARC and in the of SPARC of SPARC and the of SPARC can in and can in this the of a and a extracellular the and the SMOC-2 SMOC-2 is expressed in the expression in the and to this the for SMOC-2 is in the of of SMOC-2 in to a microarray for transcripts the SMOC-2 a cell and a for the SPARC in of in the of SMOC-2 growth and of endothelial cells in and in was was was human and was for a and SMOC-2 and and to the and adenovirus a SMOC-2 was into the of was into cells to for to the SMOC-2 adenovirus The SMOC-2 was the a a the SMOC-2 expressed the of a umbilical vein endothelial cell for a of of and to the in endothelial cell growth in the to cell to and for was and of and the for was for and to the the and was to a SMOC-2 to the was to and for was in to adenovirus for for and for was the and and a for was the a to the microarray The of and of for to and cycle of was cells for in for and in of for The cells for and a in cells and in The was to endothelial and the cells adenovirus of of and the was to and was the the was to of The for and the cells in of The of in was in of the cell and to cells of growth was the to the was and for to the and was was to the of cells of and cell was was a to the in and for in and in in was into the was in and in was also a was the of to for the of the to and to for a for adenovirus to the for cell was to the cell of the the of the a and the and the of the the of the of and was the of the cell into the was of was The culture to the The in and for a The of was and the of the cells was of of in was the a of the to of was in was to the SMOC-2 to a of of and was endothelial cell was and the The and angiogenic was cell of cells of the expressed for the of of was to of SMOC-2 in the of SMOC-2 growth of endothelial cells for SMOC-2 and SMOC-2 the a and to the cells of to the of SMOC-2 SMOC-2 was also in the culture was SMOC-2 a for of SMOC-2 transcripts in and in growth medium. in to in SMOC-2 also to determine the of a adenovirus The cells and a The of the was in to the of in the SMOC-2 a in the periphery of HUVECs. In in cells in the cell periphery and the also in cells and in the and SMOC-2 the was for and SMOC-2 is localized to the periphery and a is secreted expression is to for the factor SPARC in SMOC-2 to of the cell a for SMOC-2 a of extracellular growth factor and was was localized to the extracellular SMOC-2 was for SMOC-2 and was a was localized to the extracellular and of SMOC-2 and the is in the of SMOC-2 to the angiogenic and growth a microarray to expressed in and for in and adenovirus for cells to and to to the human of the expressed in and cells is in the was cell in transcripts and required for and of for the for and and for into In of and a of cell was in also the induced SMOC-2 expression expression of in progression of the cell transcripts of cell cycle progression and cell of cell transcripts SMOC-2 and cell in a a matricellular to and cell was SMOC-2 SMOC-2 is also a matricellular expression of transcripts cell cycle to determine and of SMOC-2 in is and of the angiogenic whether SMOC-2 cell cycle cell cycle was cell for in in cells a in the the microarray cell cycle of and in for for and was cell and in adenovirus and and for the of growth for a in and the cell of and for culture was the of human SMOC-2 and and The human SMOC-2 of the of was and was to determine The was also in in for for and in the of cell of the and for culture was the also the of for to cell cycle The of for in the of to of a in in to and adenovirus and growth factor cells a to in of and a of was to in the in of the and was of growth of the in and was the and growth factor the was is a of was a and the and growth factor the was is a The of was cell in a the of cells culture in the of and cells was in the of of SMOC-2 in was SMOC-2 the of SMOC-2 in the of was of the of a in SMOC-2 a in SMOC-2 and a was for SMOC-2 the of SMOC-2 SMOC-2 a of this was the to a in in the SMOC-2 determine the of SMOC-2 into cell cell in of growth SMOC-2 a in and the to angiogenic growth and is a of the angiogenic in a for SMOC-2 a novel angiogenic to for angiogenic activity of the of endothelial cells to the of in and in is of the angiogenic of a the of SMOC-2 of a a and a cell In the the of cells in a to in cells the of cells the of of in the of of was a adenovirus of and for for a and The cells in the of experiments, in the of was the cell was cells into the and The the of the cell the The of the cells was in of and is in the the of was also in a in the of and a to into the in the of cells and of the cell the of cells and and in to the angiogenic of to in and the cells and the of in The of the of in cells of The of to the cells also the of to in cells the cells the of angiogenic activity in a in cells in the of the of cells and also the of SMOC-2 in SMOC-2 in HUVECs. SMOC-2 in the of and in the of SMOC-2 for in in of for of the of The was the was in to whether SMOC-2 can in in the to in the of for In this the a for the and cells the and the cell of was of The of to the of cells into the in the of and The of the of cells in the and the of to the the of cells the of The cells in the to of SMOC-2 growth angiogenic activity in cultured cells and in in cell into in for of cell in in of for the SMOC-2 and a growth and angiogenic a for SMOC-2 in of angiogenesis. SMOC-2 is in endothelial cells SMOC-2 and endothelial cells in and of endothelial cells in SMOC-2 in and in SMOC-2 the of a factor SMOC-2 extracellular angiogenic growth and Consistent this SMOC-2 and and angiogenesis. and SMOC-2 is expressed in the cell periphery and is also secreted into the extracellular medium. the of SMOC-2 is in of angiogenic extracellular a of of SMOC-2 is required for the is for cell growth in the is the and is to growth factor is SMOC-2 to angiogenic to the cell and of is SMOC-2 angiogenic and of is a cell for SMOC-2 angiogenic and to for of growth factor the matricellular is also secreted and to and growth to of the growth factor family is SMOC-2 of growth factor to SMOC-2 to modulate angiogenesis. SPARC in the angiogenic activity in cell The angiogenic activity of SPARC is the growth of the in SPARC to In of this in SPARC of a is is SMOC-2 the to growth factor is a for of of growth factor expression is in cells and is cell cycle cells for and cell cycle a to In microarray of SMOC-2 the expression of cell cycle progression in growth SMOC-2 also cells and to cells to extracellular and growth and and and to growth in expression of SMOC-2 to growth and of to determine SMOC-2 is in and to a novel matricellular can endothelial cell angiogenic activity in and in cells a in a in to tissue and growth the endothelial cells and the extracellular can angiogenesis. SMOC-2 a novel for in growth and to of growth factor the of is a in and in the of the to in the of this growth and extracellular the matricellular in in and angiogenesis. extracellular to the extracellular cells and the extracellular matricellular the and the SPARC secreted and in growth endothelial growth growth secreted SMOC-2 and to of human endothelial cell growth human umbilical vein endothelial endothelial secreted and in growth endothelial growth growth secreted SMOC-2 and to of human endothelial cell growth human umbilical vein endothelial endothelial and in family of proteins. expressed in cell and expressed and is tissue SPARC is expressed and expression in is expressed in and tissue and for SPARC to a and in In the of SPARC cell to cell to the extracellular and cell SPARC cell cycle progression and to and extracellular and a in the of SPARC to growth and growth factor and endothelial growth factor SPARC the of growth factor and growth factor is SPARC is for angiogenesis. is the in is cell into is also the of SPARC and in the of SPARC of SPARC and the of SPARC can in and can in this the of a and a extracellular the and the SMOC-2 SMOC-2 is expressed in the expression in the and to this the for SMOC-2 is in the of of SMOC-2 in to In a microarray for transcripts the SMOC-2 a cell and a for the SPARC in of in the of SMOC-2 growth and of endothelial cells in and in was was was human and was for a and SMOC-2 and and to the and adenovirus a SMOC-2 was into the of was into cells to for to the SMOC-2 adenovirus The SMOC-2 was the a a the SMOC-2 expressed the of a umbilical vein endothelial cell for a of of and to the in endothelial cell growth in the to cell to and for was and of and the for was for and to the the and was to a SMOC-2 to the was to and for was in to adenovirus for for and for was the and and a for was the a to the microarray The of and of for to and cycle of was cells for in for and in of for The cells for and a in cells and in The was to endothelial and the cells adenovirus of of and the was to and was the the was to of The for and the cells in of The of in was in of the cell and to cells of growth was the to the was and for to the and was was to the of cells of and cell was was a to the in and for in and in in was into the was in and in was also a was the of to for the of the to and to for a for adenovirus to the for cell was to the cell of the the of the a and the and the of the the of the of and was the of the cell into the was of was The culture to the The in and for a The of was and the of the cells was of of in was the a of the to of was in was to the SMOC-2 to a of of and was endothelial cell was and the The and angiogenic was cell of cells of the expressed for the of of was to was was was human and was for a and SMOC-2 and and to the and adenovirus a SMOC-2 was into the of was into cells to for to the SMOC-2 adenovirus The SMOC-2 was the a a the SMOC-2 expressed the of a umbilical vein endothelial cell for a of of and to the in endothelial cell growth in the to cell to and for was and of and the for was for and to the the SMOC-2 and was to a SMOC-2 to the was to and for was in to adenovirus for for and for was the and and a for was the a to the microarray The of and of for to and cycle of was cells for in for and in of for The cells for and a in cells and in The was to endothelial and the cells adenovirus of of and the was to and was the the was to of The for and the cells in of The of in was in of the cell and to cells of growth was the to the was and for to the and was was to the of cells of and cell was was a to the in and for in and in in was into the was in and in was also a was the of to for the of the to and to for a for adenovirus to the for cell was to the cell of the the of the a and the and the of the the of the of and was the of the cell into the was In of was The culture to the The in and for a The of was and the of the cells was of of in was the a of the to of was in was to the SMOC-2 to a of of and was endothelial cell was and the The and angiogenic was cell of cells of the expressed for the of of was to of SMOC-2 in the of SMOC-2 growth of endothelial cells for SMOC-2 and SMOC-2 the a and to the cells of to the of SMOC-2 SMOC-2 was also in the culture was SMOC-2 a for of SMOC-2 transcripts in and in growth medium. in to in SMOC-2 also to determine the of a adenovirus The cells and a The of the was in to the of in the SMOC-2 a in the periphery of HUVECs. In in cells in the cell periphery and the also in cells and in the and SMOC-2 the was for and SMOC-2 is localized to the periphery and a is secreted expression is to for the factor SPARC in SMOC-2 to of the cell a for SMOC-2 a of extracellular growth factor of SMOC-2 to the angiogenic and growth a microarray to expressed in and for in and adenovirus for cells to and to to the human of the expressed in and cells is in the was cell in transcripts and required for and of for the for and and for into In of and a of cell was in also the induced SMOC-2 expression expression of in progression of the cell transcripts of cell cycle progression and cell of cell transcripts SMOC-2 and cell in a a matricellular to and cell was SMOC-2 SMOC-2 is also a matricellular expression of transcripts cell cycle to determine and of SMOC-2 in is and of the angiogenic whether SMOC-2 cell cycle cell cycle was cell for in in cells a in the the microarray cell cycle of and in for for and was cell and in adenovirus and and for the of growth for a in and the cell of and for culture was the of human SMOC-2 and and The human SMOC-2 of the of was and was to determine The was also in in for for and in the of cell of the and for culture was the also the of for to cell cycle The of for in the of to of a in in to and adenovirus and growth factor cells a to in of and a of was to in the in of the and was of growth of the in and was the and growth factor the was is a of was a and the and growth factor the was is a The of was cell in a the of cells culture in the of and cells was in the of of SMOC-2 in was SMOC-2 the of SMOC-2 in the of was of the of a in SMOC-2 a in SMOC-2 and a was for SMOC-2 the of SMOC-2 SMOC-2 a of this was the to a in in the SMOC-2 determine the of SMOC-2 into cell cell in of growth SMOC-2 a in and the to angiogenic growth and is a of the angiogenic in a for SMOC-2 a novel angiogenic to for angiogenic activity of the of endothelial cells to the of in and in is of the angiogenic of a the of SMOC-2 of a a and a cell In the the of cells in a to in cells the of cells the of of in the of of was a adenovirus of and for for a and The cells in the of experiments, in the of was the cell was cells into the and The the of the cell the The of the cells was in of and is in the the of was also in a in the of and a to into the in the of cells and of the cell the of cells and and in to the angiogenic of to in and the cells and the of in The of the of in cells of The of to the cells also the of to in cells the cells the of angiogenic activity in a in cells in the of the of cells and also the of SMOC-2 in SMOC-2 in HUVECs. SMOC-2 in the of and in the of SMOC-2 for in in of for of the of The was the was in to whether SMOC-2 can in in the to in the of for In this the a for the and cells the and the cell of was of The of to the of cells into the in the of and The of the of cells in the and the of to the the of cells the of The cells in the to of SMOC-2 growth angiogenic activity in cultured cells and in in cell into in for of cell in in of for of SMOC-2 in the of SMOC-2 growth of endothelial cells for SMOC-2 and SMOC-2 the a and to the cells of to the of SMOC-2 SMOC-2 was also in the culture was SMOC-2 a for of SMOC-2 transcripts in and in growth medium. in to in SMOC-2 also to determine the of a adenovirus The cells and a The of the was in to the of in the SMOC-2 a in the periphery of HUVECs. In in cells in the cell periphery and the also in cells and in the and SMOC-2 the was for and SMOC-2 is localized to the periphery and a is secreted expression is to for the factor SPARC in SMOC-2 to of the cell a for SMOC-2 a of extracellular growth factor of SMOC-2 to the angiogenic and growth a microarray to expressed in and for in and adenovirus for cells to and to to the human of the expressed in and cells is in the was cell in transcripts and required for and of for the for and and for into In of and a of cell was in also the induced SMOC-2 expression expression of in progression of the cell transcripts of cell cycle progression and cell a matricellular to and cell was SMOC-2 SMOC-2 is also a matricellular expression of transcripts cell cycle to determine and of HUVECs. SMOC-2 in is and of the angiogenic whether SMOC-2 cell cycle cell cycle was cell for in in cells a in the the microarray also the of for to cell cycle The of for in the of to of a in in to and adenovirus and growth factor cells a to in of and a of was to in the in of the and was of growth of the in and was the and growth factor the was is a of was a and the and growth factor the was is a The of was cell in a the of cells culture in the of and cells was in the of The of SMOC-2 in was SMOC-2 the of SMOC-2 in the of was of the of a in SMOC-2 a in SMOC-2 and a was for SMOC-2 the of SMOC-2 SMOC-2 a of this was the to a in in the SMOC-2 determine the of SMOC-2 into cell cell in of growth SMOC-2 a in and the to angiogenic growth and is a of the angiogenic in a for SMOC-2 a novel angiogenic to for angiogenic activity of the of endothelial cells to the of in and in is of the angiogenic of a the of SMOC-2 of a a and a cell In the the of cells in a to in cells the of cells the of of in the of The of was also in a in the of and a to into the in the of cells and of the cell the of cells and SMOC-2 and in to the angiogenic of to in and the cells and the of in The of the of in cells of The of to the cells also the of to in cells the cells the of angiogenic activity in a in cells in the of the of cells and also the of SMOC-2 in SMOC-2 in HUVECs. SMOC-2 in the of and in the of SMOC-2 for in was in to whether SMOC-2 can in in the to in the of for In this the a for the and cells the and the cell of was of The of to the of cells into the in the of and The of the of cells in the and the of to the the of cells the of The cells in the to of SMOC-2 growth angiogenic activity in cultured cells and in the SMOC-2 and a growth and angiogenic a for SMOC-2 in of angiogenesis. SMOC-2 is in endothelial cells SMOC-2 and endothelial cells in and of endothelial cells in SMOC-2 in and in SMOC-2 the of a factor SMOC-2 extracellular angiogenic growth and Consistent this SMOC-2 and and angiogenesis. and SMOC-2 is expressed in the cell periphery and is also secreted into the extracellular medium. the of SMOC-2 is in of angiogenic extracellular a of of SMOC-2 is required for the is for cell growth in the is the and is to growth factor is SMOC-2 to angiogenic to the cell and of is SMOC-2 angiogenic and of is a cell for SMOC-2 angiogenic and to for of growth factor the matricellular is also secreted and to and growth to of the growth factor family is SMOC-2 of growth factor to SMOC-2 to modulate angiogenesis. SPARC in the angiogenic activity in cell The angiogenic activity of SPARC is the growth of the in SPARC to In of this in SPARC of a is is SMOC-2 the to growth factor is a for of of growth factor expression is in cells and is cell cycle cells for and cell cycle a to In microarray of SMOC-2 the expression of cell cycle progression in growth SMOC-2 also cells and to cells to extracellular and growth and and and to growth in expression of SMOC-2 to growth and of to determine SMOC-2 is in and to a novel matricellular can endothelial cell angiogenic activity in and in cells a in a in to tissue and growth the endothelial cells and the extracellular can angiogenesis. SMOC-2 a novel for in growth and to of growth factor the SMOC-2 and a growth and angiogenic a for SMOC-2 in of angiogenesis. SMOC-2 is in endothelial cells SMOC-2 and endothelial cells in and of endothelial cells in SMOC-2 in and in SMOC-2 the of a factor angiogenesis. SMOC-2 extracellular angiogenic growth and Consistent this SMOC-2 and and angiogenesis. and SMOC-2 is expressed in the cell periphery and is also secreted into the extracellular medium. the of SMOC-2 is in of angiogenic extracellular a of of SMOC-2 is required for the is for cell growth in the is the and is to growth factor is SMOC-2 to angiogenic to the cell and of is SMOC-2 angiogenic and of is a cell for SMOC-2 angiogenic and to for of growth factor the matricellular is also secreted and to and growth to of the growth factor family is SMOC-2 of growth factor to SMOC-2 to modulate angiogenesis. SPARC in the angiogenic activity in cell The angiogenic activity of SPARC is the growth of the in SPARC to In of this in SPARC of a is is SMOC-2 the to growth factor is a for of of growth factor expression is in cells and is cell cycle cells for and cell cycle a to In microarray of SMOC-2 the expression of cell cycle progression in growth SMOC-2 also cells and to cells to extracellular and growth and and and to growth in expression of SMOC-2 to growth and of to determine SMOC-2 is in and to In a novel matricellular can endothelial cell angiogenic activity in and in cells a in a in to tissue and growth the endothelial cells and the extracellular can angiogenesis. SMOC-2 a novel for in growth and to of growth factor

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