Major advances in the understanding of carcinoma of the exocrine pancreas (pc) could be spawned by novel means of classifying pc specimens according to (1) normal cell of origin and (2) degree of differentiation. The goal of this proposal is to establish a family of cell adhesion receptors, the integrins, as molecular markers for staging pc, by exploiting their property of being expressed in cell- specific, structurally distinct forms. Integrins form a complex system of structurally related but nonidentical surface glycoproteins. Because of their indispensable role in cell adhesion, integrins are found virtually on all cells, normal and malignant. However, a considerable body of evidence suggests that distinct mosaics of structurally distinct integrins are expressed by a cell depending upon its tissue of origin and its stage of differentiation. These cell-specific expression differences make integrins ideal candidates to serve as molecular markers in pc. Our plan is to isolate molecular clones of the integrin forms expressed by pc tissues and, based on their structures, construct highly discriminating antibody and nucleic acid probes. Screening of pc tissues will establish recurrent patterns of integrin expression. Matching these patterns with those of normal pancreatic cells may point at the cell of origin of pc specimens, while clustering them may reveal distinct differentiation groups. Efforts will then be made to correlate these parameters with pathological manifestations and metastasis. This information may result in effective ways for staging pancreatic cancer, hopefully offering new perspectives on carcinogenesis risk and treatment regimens of this disease.
