Inhibition of breast cancer progression by an antibody to a thrombospondin-1 receptor.
BACKGROUND
Thrombospondin-1 (TSP-1) is a matrix-bound adhesive glycoprotein. Breast carcinoma cells exhibit increased expression of a novel TSP-1 receptor. We evaluated the role of this receptor in breast cancer adhesion and progression.


METHODS
Adhesion assays were performed to evaluate MDA-MB-231 breast cancer cell adhesion to TSP-1 in vitro in the presence of either nonimmune immunoglobulin G(IgG) or anti-TSP-1 receptor IgG. Receptor-mediated tumor cell progression was evaluated in athymic nude mice. Mice were inoculated with MDA-MB-231 breast cancer cells and randomized to treatment with intraperitoneal injections of saline solution, nonspecific IgG antibody, or an anti-TSP-1 receptor antibody every other day for 20 days. Mice were killed at 21 days. The peritoneal cavity was examined grossly for primary tumor implantation. The liver and lungs were examined histologically for micrometastases.


RESULTS
MDA-MB-231 breast cancer cells adhered to TSP-1 in vitro. This adhesion was inhibited to 10% of control by anti-TSP-1 receptor antibody (p < 0.005). Anti-TSP-1 receptor antibody inhibited in vivo breast cancer progression. Mice treated with control IgG antibody or saline solution alone exhibited extensive intraperitoneal seeding. Only one mouse treated with the anti-TSP-1 receptor antibody exhibited any intraperitoneal tumor seeding (p < 0.01).


CONCLUSIONS
These data suggest that TSP-1 and its receptor play an important role in breast cancer progression.
Wang
T N
TN
Department of Surgery, Medical College of Pennsylvania, Philadelphia, USA.
Qian
X H
XH
Granick
M S
MS
Solomon
M P
MP
Rothman
V L
VL
Berger
D H
DH
Tuszynski
G P
GP
D000818:Animals; D000918:Antibody Specificity; D001943:Breast Neoplasms / Q000473:pathology*; D018955:CD36 Antigens / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010534:Peritoneal Neoplasms / Q000556:secondary; D011817:Rabbits; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000166:cytology / Q000502:physiology
D018955:CD36 Antigens; D015815:Cell Adhesion Molecules