@article{a40e40aa67f14c199407a98973dbbe58,
title = "Inhibition of breast cancer progression by an antibody to a thrombospondin-1 receptor",
abstract = "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 ith 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.",
author = "Wang, {T. N.} and X. Qian and Granick, {M. S.} and Solomon, {M. P.} and Rothman, {V. L.} and Berger, {D. H.} and Tuszynski, {G. P.}",
note = "Funding Information: THROMBOSPONDIN-I (TSP-1), one of four structurally related proteins encoded by different genes, 1 was first identified in 1971 by Baenziger et al. 2 as a high molecular weight glycoprotein released from thrombin-stimulated platelets. TSP-I is composed of three identical disulfide-linked chains, each consisting of 1152 amino acids (molecular weight, 145,000 d).3 TSP-1 is produced by a variety of cell types including endothelial cells, 4 fibroblasts, 5 macrophages, monocytes, 6 and tumor cells. 7 Most of the TSP-1 produced by these cells are bound to the extracellular matrix and associated strongly with the basement membrane, s Functionally, TSP-1 is an adhesive protein that promotes cell-cell and cell-matrix interactions of normal cells and malignant cells. 9' 10 Supported in part by National Institutes of Health grants CA65675 and CA69722. Presented at the Fifty-seventhA nnual Meeting of the Society of University Surgeons, Washington, D.C., Feb. 8-10, 1996. Reprint requests: George P. Tuszynski, PhD, Department of Surgery, The Medical College of Pennsylvania and Hahnemann University, 2900 Queen Lane, Philadelphia, PA 19129. Copyright 9 1996 by Mosby-YearB ook, Inc. 0039-6060/96/$5.00 + 0 11/6/73723 TSP-1 also promotes platelet aggregation ll and mediates angiogenesis. 12' 13 A growing body of evidence has implicated TSP-1 in human tumor invasion and metastasis. In vitro TSP-1 promotes tumor cell adhesion and motility and up-regulates plasminogen activator enzymes (plasminogen activator inhibitor type 1 and urokinase-type plasminogen activator).14 Our laboratory has shown that TSP-1 promotes in vitro tumor cell invasion of collagen in three different breast cancer cell lines. 15 In vivo TSP-1 potentiates lung metastasis in an intravenous murine sarcoma model. 16 It has been shown that patients with breast, lung, colon, and gynecologic malignancies have significantly elevated serum levels of TSP-1 compared with non-tumor-bearing human controls. 17 Furthermore, human malignant breast tumors have been shown to have large amounts of TSP-1 within the tumor stroma compared with benign breast tumors. TM Finally, our laboratory has shown that a novel TSP-1 receptor is over-expressed in several types of human invasive tumors, TM including breast cancers (Fig. 1).",
year = "1996",
doi = "10.1016/S0039-6060(96)80322-9",
language = "English (US)",
volume = "120",
pages = "449--454",
journal = "Surgery",
issn = "0039-6060",
publisher = "Mosby Inc.",
number = "2",
}