Breast cancer cell-derived fibroblast growth factor 2 and vascular endothelial growth factor are chemoattractants for bone marrow stromal stem cells.
OBJECTIVE
Recent efforts by the scientific community to characterize the complex interplay between different cell types involved in the development of tumors have led us to investigate the roles of vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2) in the development of breast cancer.


METHODS
Using modified Boyden chamber assays, we measured the in vitro migration effect on murine mesenchymal stem cells (MSCs). Additionally, we assayed for the presence of receptors for these growth factors on MSCs, and for the presence of VEGF and FGF2 in breast cancer-conditioned media. We measured the change in migration of MSCs toward breast cancer when we depleted these growth factors from breast cancer-conditioned media. Further, we conducted a series of standard curve migration assays for basal media supplemented with physiologic concentrations of VEGF and FGF2.


RESULTS
Analysis of gene expression and protein analysis demonstrated the expression of FGF2 and VEGF by the breast cancer cells, and the presence of VEGF (FLK1) and FGF2 receptors on the MSCs. We also demonstrated a reduction in migration when we antibody-depleted VEGF and FGF2 from breast cancer-conditioned media. Additionally, we found the physiologic concentrations of VEGF and FGF2 at 12 and 15 ng/mL, respectively.


CONCLUSIONS
We demonstrate that VEGF and FGF2 induce migration of MSCs are secreted by breast cancer cells, their receptors are present on MSCs, and depletion of these growth factors reduces migration, and are therefore 2 relevant growth factors for MSC migration toward breast cancer cells.
Ritter
Edmond
E
Department of Surgery, School of Medicine, Medical College of Georgia, Augusta, Georgia 30912, USA. eritter@mcg.edu
Perry
Adam
A
Yu
Jack
J
Wang
Thomas
T
Tang
Lawton
L
Bieberich
Erhard
E
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D002630:Chemotactic Factors / Q000235:genetics / Q000378:metabolism; D017077:Culture Media, Conditioned; D004195:Disease Models, Animal; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D012334:RNA, Neoplasm / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
D002630:Chemotactic Factors; D017077:Culture Media, Conditioned; D012334:RNA, Neoplasm; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2