DIFFERENTIAL HSP70 PLASMA-MEMBRANE EXPRESSION ON PRIMARY HUMAN TUMORSAND METASTASES IN MICE WITH SEVERE COMBINED IMMUNODEFICIENCY

To study the role of cell-surface expression of a tumor-elective heat- shock protein 70 (Hsp70) in vivo, the colon-carcinoma cell line CX2, a nd the clonal sub-lines CX+ and CX-, which differ in Hsp70 cell-surfac e expression, but not in MHC and adhesion-molecule expression, were im planted into immunodeficient SCID/beige mice by s.c., i.p., i.v. and o rthotopic (o.t.) inoculation. On day is after s.c. injection, all anim als developed s.c. tumors, ranging in size from 2.5 to 3 cm(2). Phenot ypic characterization of single-cell suspensions generated from freshl y isolated tumor material revealed that the pattern of cell-surface ex pression is identical to that of the injected tumor cells from cell cu lture. Comparable results were obtained following i.p. inoculation of CX+ and CX- cells. Macroscopic and microscopic evaluation of lymph nod es, lung, liver and spleen at autopsy of tumor-bearing mice showed no tumor burden except the primary tumor, following s.c. or i.p. injectio n. After i.v. inoculation of CX+ and of CX- cells, weak tumor growth w as observed in lung and liver, the Hsp70 cell-surface-expression patte rn on these tumors being identical to that of the injected cells. Howe ver, o.t. injection of colon-carcinoma cell lines CX+ and CX- into the cecum resulted in tumor growth at the injection site and in spread of distant metastases in lung, liver and spleen. Most interestingly, and in contrast to the primary colon carcinomas, metastases of CX+ and of CX- tumor cells both revealed strong Hsp70 plasma-membrane expression , although the total amount of cytoplasmic Hsp70 was comparable. (C) 1 998 Wiley-Liss, Inc.