The present invention provides compositions and methods for treating a tissue
disorder associated with a response-to-injury process or proliferating cells in
a mammal. These tissue disorders are associated with a novel cellular phenotype
designated as "transition cells" which are described herein. This cellular phenotype
is characterized in having an activated erk kinase signaling activity, a stimulated
AP-1 binding activity, and at least one characteristic selected from the group
consisting of: (a) increased podosome formation, (b) increased flux of intracellular
or extracellular hyaluronans or hyaladherins, (c) increased expression of a hyaladherin,
(d) an inability to form focal adhesions, (e) increased metalloproteinase activity,
and (f) increased expression of a hyaladherin. Example tissue disorders include
fibrosis, inflammation, degeneration and invasive disorders such as occur in cancerous
cells. The methods provided herein include administering to the mammal, an effective
amount of a composition that alters the activity of transition molecules within
a cell Transition molecules are shown to be comprised of hyaladherins, hyaluronans
and associated molecules that regulate the transitional phenotype. A novel cell
culture comprising transition cells is also provided, as well as compositions comprising
particular peptides, polypeptides, and antibodies that affect the transitional phenotype.
