DIFFERENTIAL EXPRESSION OF THE H-2D(K) MHC CLASS-I ANTIGEN AND TISSUEINHIBITOR OF METALLOPROTEINASES IN METASTATIC AND NONMETASTATIC T-10 FIBROSARCOMA CELLS

In previous studies, we have demonstrated that the highly metastatic I E-7 cell clone, derived from the T-10 fibrosarcoma, expressed both the H-2D(k) and H-2D(b) genes, whereas a nonmetastatic IC-9 clone, derive d from the same tumor, expressed only H-2D(b), Suggesting that the H-2 D(k) product might be involved in the metastatic phenotype. To substan tiate this notion, IC-9 cells were transfected with an H-2D(k)-express ing vector. Although all of the 4 randomly selected transfectant subcl ones elicited high H-2D(k) expression, only one was as metastatic as I E-7 cells. This metastatic transfectant resembled IE-7 cells also in i ts inability to evoke CTL response in syngeneic mice, whereas the othe r transfectants were quite competent in this respect. It thus appears that the H-2D(k) product, may contribute to the metastatic phenotype p rovided that it is immunogenically abnormal. In addition, the present study provides evidence to suggest that lack of production of the tiss ue inhibitor of metalloproteinases TIMP-1/TIMP-2 is another important determinant in the metastatic phenotype of these cells.