Truncated 24kDa basic fibroblast growth factor
The invention relates to fragments of an amino acid sequence of mature, full length 24 kDa fibroblast growth factor-2 or an analog thereof. The fragments have an activity that inhibits the migration of cultured cells as well as inhibiting angiogenesis, tumor growth, or any other processes that involve the migration of cells in vivo. This fragment does not stimulate the proliferation of cells which is in contrast to activity shown by the mature, full-length 24 kDa fibroblast growth factor-2. The present invention also relates to a DNA molecule encoding the fragment, an expression vector and a transformed host containing the DNA molecule, and a method of producing the protein by culturing the transformed host. Moreover, the present invention relates to a therapeutic composition the 24 kDa fibroblast growth factor fragment and a pharmaceutically acceptable carrier.
1. A method of treatment comprising:
a) providing a patient having a disease or condition associated with undesired cell migration, invasion, migration-induced proliferation, or angiogenesis;
b) providing a pharmaceutical composition comprising the polypeptide of SEQ ID NO: 2, wherein said polypeptide has at least one of anti-angiogenic, tumor-suppressive, or anti-migratory activity, but does not have stimulation of cell proliferation activity; and
c) administering said pharmaceutical composition to said patient.
2. The method of treatment of claim 1 , wherein said disease or condition is one or more diseases or conditions selected from the group consisting of tumor growth, tumor invasion or metastasis, mammary carcinoma, lung carcinoma, atherosclerosis, post-balloon angioplasty vascular restenosis, neointima formation following vascular trauma, vascular graft restenosis, fibrosis associated with a chronic inflammatory condition, lung fibrosis, chemotherapy-induced fibrosis, wound healing with scarring and fibrosis, psoriasis, deep venous thrombosis, retinopathy, and disease or any condition in which angiogenesis is pathogenic.
3. The method of treatment of claim 1 , wherein said pharmaceutical composition is administered by one or more routes selected from the group consisting of oral, parenteral, intraperitoneal, transdermal, topical, inhalation, and injection by either subcutaneous, intravenous, or intramuscular administration.
4. A method of treatment comprising:
a) providing a patient having a disease or condition associated with undesired cell migration, invasion, migration-induced proliferation, or angiogenesis;
b) providing a pharmaceutical composition comprising a polypeptide that comprises an amino acid sequence that differs from the amino acid sequence of SEQ ID NO: 2 by one or more conservative amino acid substitutions, wherein said polypeptide has at least one of anti-angiogenic, tumor-suppressive, or anti-migratory activity, but does not have stimulation of cell proliferation activity; and
c) administering said pharmaceutical composition to said patient.
5. The method of treatment of claim 4 , wherein said disease or condition is one or more diseases or conditions selected from the group consisting of tumor growth, tumor invasion or metastasis, mammary carcinoma, lung carcinoma, atherosclerosis, post-balloon angioplasty vascular restenosis, neointima formation following vascular trauma, vascular graft restenosis, fibrosis associated with a chronic inflammatory condition, lung fibrosis, chemotherapy-induced fibrosis, wound healing with scarring and fibrosis, psoriasis, deep venous thrombosis, retinopathy, and disease or any condition in which angiogenesis is pathogenic.
6. The method of treatment of claim 4 , wherein said pharmaceutical composition is administered by one or more routes selected from the group consisting of oral, parenteral, intraperitoneal, transdermal, topical, inhalation, and injection by either subcutaneous, intravenous, or intramuscular administration.