Thrombospondin-1 (TSP-1) promotes the invasive properties of human breast cancer.
TSP-1 is a matrix-bound adhesive glycoprotein, which plays a role in tumor cell proliferation and tumor angiogenesis. The purpose of this study was to investigate the effect of TSP-1 on breast tumor cell invasion. Tumor cell invasion assays were performed using a modified Boyden chamber apparatus with collagen-coated membranes. Four breast cell lines were studied in serum-free media: the malignant MDA-MB-231, SKBR-3, and MCF-7 cell lines, and the benign MCF-10A cell line. Invasion was measured as the summation of the number of cells in five representative high power fields (400x) traversing the collagen barrier after a 3-hr incubation period. The effect of an anti-TSP-1 antibody (100 microgram/ml) was also evaluated in the malignant cell lines. Statistical analysis was performed by ANOVA and Student's unpaired t test. TSP-1 promoted a dose-dependent increase in invasion as compared to buffer controls in all three malignant cell lines. TSP-1 (100 nM) promoted a greater than five-fold increase over controls in tumor cell invasion for MDA-MB-231, SKBR-3, and MCF-7 cell lines (P < 0.005). TSP-1 had no effect on the invasiveness of the benign cell type MCF-10A. Anti-TSP-1 antibody inhibited TSP-1 promoted invasion in the MDA-MB-231, SKBR-3, and MCF-7 cell lines by 45, 48, and 39%, respectively (P = 0.003, 0.044, 0.047). TSP-1 promotes tumor cell invasion of collagen by breast cancer cells. Therapy designed to inhibit TSP-1 may prevent invasion and metastasis in breast cancer.
Wang
T N
TN
Department of Surgery, Medical College of Pennsylvania and Hahnemann University, Philadelphia 19129, USA.
Qian
X
X
Granick
M S
MS
Solomon
M P
MP
Rothman
V L
VL
Berger
D H
DH
Tuszynski
G P
GP
D000704:Analysis of Variance; D000906:Antibodies / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000494:pharmacology / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003094:Collagen; D005260:Female; D006801:Humans; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000276:immunology / Q000494:pharmacology* / Q000502:physiology*; D009361:Neoplasm Invasiveness; D019699:Thrombospondins; D014407:Tumor Cells, Cultured
D000906:Antibodies; D015815:Cell Adhesion Molecules; D008562:Membrane Glycoproteins; D019699:Thrombospondins; D003094:Collagen