University of Michigan

Stephen J Weiss

David Thomas Dudley

Robert G Rowe

The invention provides an integrin alpha-2 binding agent and methods of using an integrin alpha-2 binding agent to, e.g., inhibit proliferation of cancer cells, modulate tumor growth in a subject, inhibiting angiogenesis, or treating a fibrotic disorder. The invention further provides a method of producing an antibody, the method comprising propagating cancer cells in a 3-dimensional matrix; immunizing a mammal with the propagated cancer cells; and isolating an antibody from the immunized mammal. A method of identifying an agent that inhibits cancer cell proliferation also is provided.

Integrin alpha-2 binding agents and use thereof to inhibit cancer cell proliferation

The invention provides a method of inhibiting neovascularization in a subject. The method comprises administering to the subject an agent that interferes with fibronectin (Fn) matrix assembly in an amount effective to inhibit neovascularization. The invention also provides a method of identifying an agent that inhibits neovascularization. The method comprises detecting fibronectin (Fn) matrix assembly by stimulated endothelial cells cultured in three-dimensional culture gel in the presence and absence of an agent. A decrease in Fn matrix assembly in the presence of the agent compared to Fn matrix assembly in the absence of the agent is indicative of an agent that inhibits neovascularization. Alternatively, the method of identifying an agent that inhibits neovascularization comprises detecting changes in nuclear architecture in stimulated endothelial cells cultured in three-dimensional culture gel in the presence and absence of an agent. A reduction in nuclear architecture organization identifies an agent that inhibits neovascularization.

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Ann Arbor, MI, United States of America

Stephen J Weiss