La Jolla Cancer Research Foundation

The Burnham Institute

Yu Yamaguchi

Erkki I Ruoslahti

Wayne A Border

Motoyuki Shimonaka

The present invention provides methods of treating pathologies using Decorin.

Methods of treating a pathology or a fibrotic condition by administering decorin

The present invention provides a method of inhibiting an activity of a cell regulatory factor comprising contacting the cell regulatory factor with a purified polypeptide, wherein the polypeptide comprises the cell regulatory factor binding domain of a protein and wherein the protein is characterized by a leucine-rich repeat of about 24 amino acids. In a specific embodiment, the present invention relates to the ability of decorin, a 40,000 dalton protein that usually carries a glycosaminoglycan chain, to bind TGF-&bgr;. The invention also provides a novel cell regulatory factor designated MRF. Also provided are methods of identifying, detecting and purifying cell regulatory factors and proteins which bind and affect the activity of cell regulatory factors. The present invention further relates to methods for the prevention or reduction of scarring by administering decorin or a functional equivalent of decorin to a wound. The methods are particularly useful for dermal wounds resulting from burns, injuries or surgery. In addition, the present invention includes pharmaceutical compositions containing decorin or its functional equivalent and a pharmaceutically acceptable carrier useful in such methods. Finally, methods for preventing or inhibiting pathological conditions by administering decorin are also provided.

Methods for inhibiting TGF-&bgr; activity

A method of suppressing cell proliferation of a mammalian cell by contacting the cell with decorin.

Suppression of cell proliferation by decorin

A method of treating of glomerulonephritis in a patient by administering decorin.

Treatment of glomerulonephritis with decorin

The present invention provides a substantially purified polypeptide, epitaxin, which is produced by fibroblasts and can stimulate migration of and DNA synthesis in a tumor cell. The invention also provides antibodies that are specifically reactive with epitaxin and cell lines that produce such antibodies. The invention also provides an active fragment antagonist of ETX activity, which can reduce or inhibit at least one activity of ETX. The invention further provides a method for controlling tumor cell migration and a method for controlling DNA synthesis in a tumor cell, comprising contacting the tumor cell with a composition of the invention. The invention also provides a method of increasing the sensitivity of a tumor cell to a cancer therapeutic agent.

Epitaxin, a cell motility factor

The present invention provides a method of inhibiting an activity of TGF.beta. comprising contacting the TGF.beta. with a purified decorin. In a specific embodiment, the present invention relates to the ability of decorin, a 40,000 dalton protein that usually carries a glycosaminoglycan chain, to bind TGF.beta.. The invention also provides a novel cell regulatory factor designated MRF. Also provided are methods of identifying, detecting and purifying cell regulatory factors and proteins which bind and affect the activity of cell regulatory factors.

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San Diego, CA, United States of America

Yu Yamaguchi