Breast cancer cells secreted platelet-derived growth factor-induced motility of vascular smooth muscle cells is mediated through neuropilin-1.
Motility of vascular smooth muscle cells (SMCs) is an essential step for both normal and pathologic angiogenesis. We report here that breast tumor cells, such as MCF-7 and MDA-MB-231, can modulate this SMC migration. We present evidence that the tumor cell-derived platelet-derived growth factor (PDGF) is the key regulator of vascular SMCs motility induced by breast cancer cells. PDGF significantly upregulates neuropilin-1 (NRP-1) mRNA expression and protein production in aortic smooth muscle cells (AOSMCs) and depletion of NRP-1 production by AOSMCs with specific short hairpin RNA (shRNA) prevents the PDGF-dependent migration of vascular SMCs. Moreover, we demonstrate that PDGF physically interacts with NRP-1. We propose that tumor-derived PDGF and NRP-1 of AOSMCs function as a relay system that promotes motility of vascular SMCs.
Banerjee
Snigdha
S
Cancer Research Unit, VA Medical Center, Kansas City, Missouri 64128, USA.
Sengupta
Krishanu
K
Dhar
Kakali
K
Mehta
Smita
S
D'Amore
Patricia A
PA
Dhar
Gopal
G
Banerjee
Sushanta K
SK
D001483:Base Sequence; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D017931:DNA Primers; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D039942:Neuropilin-1 / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017077:Culture Media, Conditioned; D017931:DNA Primers; D010982:Platelet-Derived Growth Factor; D039942:Neuropilin-1