TY - JOUR
T1 - Stromal cell-derived factor-1 stimulates vasculogenesis and enhances Ewing's sarcoma tumor growth in the absence of vascular endothelial growth factor
AU - Reddy, Krishna
AU - Zhou, Zhichao
AU - Jia, Shu Fang
AU - Lee, Tim H.
AU - Morales-Arias, Jaime
AU - Cao, Ying
AU - Kleinerman, Eugenie S.
PY - 2008/8/15
Y1 - 2008/8/15
N2 - Stromal cell-derived Factor-1α (SDF-1α) stimulates the migration of bone marrow (BM) cells, similar to vascular endothelial growth factor (VEGF). We previously demonstrated that inhibition of VEGF165 by small interfering RNA inhibited Ewing's sarcoma tumor growth, tumor vessel formation and recruitment of BM cells to the tumor. To determine the importance of BM cells in tumor vessel development, we investigated the effects of SDF-1α on VEGF-inhibited TC/siVEGF7-1 Ewing's tumor neovasculature formation and growth. The effect of SDF-1α on CD34 + progenitor cell chemotaxis was determined in vivo. Using a BM transplantation model with GFP+ transgenic mice as BM donors and nude mice as recipients, we evaluated the effect of SDF-1α on the recruitment of BM-derived cells to VEGF165-inhibited TC/siVEGF7-1 tumors, as well as its effect on neovasculature development, vessel morphology and tumor growth. SDF-1α stimulated the migration of CD34+ progenitor cells to Matrigel plugs in vivo and promoted the retainment of BM-derived pericytes in close association with perfused, functional tumor vessels. Intratumor inoculation of Ad-SDF-1α into TC/siVEGF7-1 tumors resulted in increased SDF-1 and PDGF-BB expression, augmented tumor growth, an increase in the number of large, lumen-bearing vascular structures, and enhanced vessel pericyte coverage, with no change in VEGF165. SDF-1α stimulates BM cell chemotaxis and the association of these cells with functional tumor vessels. Furthermore, SDF-1α enhances tumor neovascularization and growth with no alteration in VEGF165. Our work suggests that SDF-1-mediated vasculogenesis may represent an alternate pathway that could potentially be utilized by tumors to sustain growth and neovasculature expansion after anti-VEGF therapy.
AB - Stromal cell-derived Factor-1α (SDF-1α) stimulates the migration of bone marrow (BM) cells, similar to vascular endothelial growth factor (VEGF). We previously demonstrated that inhibition of VEGF165 by small interfering RNA inhibited Ewing's sarcoma tumor growth, tumor vessel formation and recruitment of BM cells to the tumor. To determine the importance of BM cells in tumor vessel development, we investigated the effects of SDF-1α on VEGF-inhibited TC/siVEGF7-1 Ewing's tumor neovasculature formation and growth. The effect of SDF-1α on CD34 + progenitor cell chemotaxis was determined in vivo. Using a BM transplantation model with GFP+ transgenic mice as BM donors and nude mice as recipients, we evaluated the effect of SDF-1α on the recruitment of BM-derived cells to VEGF165-inhibited TC/siVEGF7-1 tumors, as well as its effect on neovasculature development, vessel morphology and tumor growth. SDF-1α stimulated the migration of CD34+ progenitor cells to Matrigel plugs in vivo and promoted the retainment of BM-derived pericytes in close association with perfused, functional tumor vessels. Intratumor inoculation of Ad-SDF-1α into TC/siVEGF7-1 tumors resulted in increased SDF-1 and PDGF-BB expression, augmented tumor growth, an increase in the number of large, lumen-bearing vascular structures, and enhanced vessel pericyte coverage, with no change in VEGF165. SDF-1α stimulates BM cell chemotaxis and the association of these cells with functional tumor vessels. Furthermore, SDF-1α enhances tumor neovascularization and growth with no alteration in VEGF165. Our work suggests that SDF-1-mediated vasculogenesis may represent an alternate pathway that could potentially be utilized by tumors to sustain growth and neovasculature expansion after anti-VEGF therapy.
KW - Bone marrow stem cells
KW - Ewing's sarcoma
KW - Pericytes
KW - SDF-1
KW - Vasculogenesis
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U2 - 10.1002/ijc.23582
DO - 10.1002/ijc.23582
M3 - Article
C2 - 18537159
AN - SCOPUS:47049107160
SN - 0020-7136
VL - 123
SP - 831
EP - 837
JO - International journal of cancer
JF - International journal of cancer
IS - 4
ER -