Differential expression of the H-2Dk MHC class-I antigen and tissue inhibitor of metalloproteinases in metastatic and nonmetastatic T-10 fibrosarcoma cells.
In previous studies, we have demonstrated that the highly metastatic IE-7 cell clone, derived from the T-10 fibrosarcoma, expressed both the H-2Dk and H-2Db genes, whereas a nonmetastatic IC-9 clone, derived from the same tumor, expressed only H-2Db, suggesting that the H-2Dk product might be involved in the metastatic phenotype. To substantiate this notion, IC-9 cells were transfected with an H-2Dk-expressing vector. Although all of the 4 randomly selected transfectant subclones elicited high H-2Dk expression, only one was as metastatic as IE-7 cells. This metastatic transfectant resembled IE-7 cells also in its inability to evoke CTL response in syngeneic mice, whereas the other transfectants were quite competent in this respect. It thus appears that the H-2Dk product may contribute to the metastatic phenotype provided that it is immunogenically abnormal. In addition, the present study provides evidence to suggest that lack of production of the tissue inhibitor of metalloproteinases TIMP-1/TIMP-2 is another important determinant in the metastatic phenotype of these cells.
Har-Vardi
I
I
Department of Microbiology and Immunology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
Gopas
J
J
Rager-Zisman
B
B
Hammerling
G J
GJ
Segal
S
S
Aboud
M
M
D000818:Animals; D001483:Base Sequence; D005354:Fibrosarcoma / Q000276:immunology* / Q000378:metabolism / Q000556:secondary*; D015870:Gene Expression / Q000502:physiology; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D006183:H-2 Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D064532:Histocompatibility Antigen H-2D; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D019714:Tissue Inhibitor of Metalloproteinases; D014162:Transfection / Q000235:genetics; D014407:Tumor Cells, Cultured
D006023:Glycoproteins; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019714:Tissue Inhibitor of Metalloproteinases