Culture Based Screening Assay and Methods of Use Thereof to Identify Agents Which Modulate Tumor Development, Invasion and Differentiation

A method of in vitro screening of a compound comprising

• a) incubating an organotypic culture comprising an artificial stroma including a mixture of collagen and human fibroblasts isolated from a tissue of interest, said stroma being overlayed with primary keratinocytes, said keratinocytes comprising nucleic acids encoding at least one activated oncogene and at least one inactivated tumor suppressor gene, said culture exhibiting enhanced cell migration and invasion in an artificial extracellular matrix relative to control keratinocytes which lack said nucleic acids in the presence and absence of said compound, and observing the effect of said compound upon the migration and invasive characteristics of said keratinocytes relative to cells which are not incubated with said compound.

A genetic signature associated with cells exhibiting increased invasiveness, comprising nucleic acids encoding N-cadherin, melanoma cell adhesion molecule, periostin and cadherin 11, said nucleic acids exhibiting differential expression in invading versus non-invading cells as set forth in Table 1.

An assay kit for determining the presence a genetic signature encoding proteins associated with increased tumor cell migration and invasion in a biopsy sample of esophageal cells, comprising antibodies immunologically specific for at least two proteins selected from the group consisting of cadherin 2, type 1, N cadherin, melanoma cell adhesion molecule, periostin, osteoblast specific factor, cadherin 11, type 2, OB-cadherin, claudin 1, claudin 4 claudin 7, occludin, one of said at least one protein or antibody being detectably labeled.