Thrombospondin-1 (TSP-1) is a potent inhibitor of tumor growth and
angiogenesis. To elucidate the molecular mechanisms that are involved in
the inhibition of tumor growth by the type 1 repeats (TSRs), recombinant
versions of these motifs have been produced and have been assayed for
their ability to inhibit the growth of experimental B16F10 and Lewis lung
carcinomas. Recombinant proteins that contain all three TSRs (3TSR) or
the second TSR with (TSR2+RFK) or without (TSR2) the transforming growth
factor beta (TGF.beta.) activating sequence (RFK) have been expressed in
Drosophila S2 cells. A recombinant protein containing all three type 1
repeats of TSP-2 and a recombinant protein containing the second TSR with
the RFK sequence altered to QFK have also been produced. The data
indicate that the TSRs inhibit tumor growth by inhibition of angiogenesis
and regulation of tumor cell growth and apoptosis. The regulation of
tumor cell growth and apoptosis is RFK-dependent while the inhibition of
angiogenesis is not. The invention relates to polypeptides based on the
amino acid sequence of human TSP-1 type 1 repeats. The polypeptides,
variants, fragments and mutants thereof can be made by recombinant
methods or can be made by chemical synthesis. The polypeptides can be
formulated into pharmaceutical compositions and used in methods of
therapy to reduce tumor growth.