CLONES OF TUMOR-CELLS DERIVED FROM A SINGLE PRIMARY HUMAN LUNG-TUMOR REVEAL DIFFERENT PATTERNS OF BETA(1)-INTEGRIN EXPRESSION

Previously we reported that over 75% of human non-small cell lung canc ers overexpress the beta(1) integrin VLA-2 on their surface and show a n increase in the mRNA encoding the alpha-2 chain of this integrin. Th ese results suggested the possibility that the overproduction and over expression of one or more of the beta(1) integrin may be involved in t he pathogenesis of human lung tumors by modulating the invasive and/or metastatic potential of the tumor. We report here the generation and characterization of multiple clones of tumor cells derived from the pr imary culture of cells obtained from biopsy tissue of an aggressive hu man squamous cell lung tumor. We show that these tumor clones (or clon otypes) exhibit seven different yet stable phenotypes with respect to the expression of five members of the beta(1) integrin family. These r esults illustrate that a primary human lung tumor consists of multiple subpopulations of cells that while indistinguishable by ultrastructur e are heterogeneous with respect to their beta(1) integrins. The avail ability of these distinct tumor clonotypes derived from a single tumor biopsy have made it possible to test the assumption that the beta(1) integrins play a role in tumor progression. The feasibility of this ap proach is demonstrated here by the intravenous inoculation of differen t human tumor clonotypes into severe combined immunodeficient (scid) m ice. Our preliminary results with a pair of tumor clonotypes differing in VLA-1 and VLA-2 expression level reveal that the clonotype with hi gh level of VLA-1 and VLA-2 displays a substantial increase in the exp erimental engraftment and metastasis of the human tumor cells in scid mice.