Altered establishment/clearance mechanisms during experimental micrometastasis with live and/or disabled bacterial lacZ-tagged tumor cells.
To study micrometastasis at its earliest stages, the bacterial lacZ marker gene was introduced into human EJ Ha-ras-transformed BALB/c 3T3 cells (LZEJ), followed by their intravenous injection into nude mice. Lung micrometastases were easily identified by blue staining of lacZ-tagged cells minutes/hours after injection, permitting effective evaluation of establishment/clearance mechanisms of LZEJ cells. Different treatments were used to disable LZEJ cells (fixation, irradiation, or mitomycin C) to determine modulation of these processes--although unable to divide, these cells stain for lacZ expression for days after treatment. Fixation-killed cells generated large microfoci (> 13-15 cells/focus) with well-rounded morphologies while live, irradiated, or mitomycin-treated cells generated smaller, irregularly shaped foci (3-7 cells/focus). Fixed-cell foci were cleared more slowly from lungs than the other three classes, even when prefiltered to remove large aggregates. All foci of disabled cells were eventually cleared while a basal level of live-cell foci persisted. Co-injection of fixed and live cells (or preinjection of fixed cells, followed by live cells) resulted in complete clearance of live-cell microfoci; in contrast, preinjection of live cells (then injection of fixed cells) led to survival of live-cell micrometastases. Therefore, altered deformability and/or cell surface interactions of tumor cells modulate the effectiveness of host-clearing mechanisms in the lung and in some situations these altered cells facilitate clearance of live tumor cells that are normally tumor-progressing.
Lin
W C
WC
Department of Molecular Biology and Microbiology, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106.
Culp
L A
LA
D016475:3T3 Cells / Q000502:physiology; D000818:Animals; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D005260:Female; D005798:Genes, Bacterial / Q000235:genetics; D006801:Humans; D007763:Lac Operon / Q000235:genetics*; D008175:Lung Neoplasms / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects