title: Sequential observation of micrometastasis formation by bacterial lacZ gene-tagged Lewis lung carcinoma cells.
abstract: Sequential events in micrometastasis formation including entry into the blood circulation and arrest, extravasation and initial growth in the lung was investigated using bacterial lacZ gene-tagged Lewis lung carcinoma cells (4A1-1). Micrometastases in the lung could thereby be specifically detected at the single cell level by X-Gal staining. After intravenous injection, X-Gal positive tumor cells appeared to extravasate within hours, but most cells then degenerated or died in the alveolar space by 2-3 days postinjection. A decreased BrdU labeling index to a negligible level at 2 days postinjection and reduction of X-Gal positive foci to a basal level (less than 0.1% of injected cells) by 4 days are in line with rapid clearance of tumor cells from the lung. The size and BrdU labeling indices of the persisting X-Gal positive foci, however, started to increase from 4 days postinjection. Type IV collagen immunostaining demonstrated loss of pre-existing basement membranes with growth of micrometastases: When 4A1-1 cells were inoculated subcutaneously, lung micrometastases from resulting tumors were detected as single or small numbers of X-Gal positive cells at 2 weeks postinjection. Progressive development of micrometastasis to macroscopic metastasis was noted by 4-5 weeks postinjection. The results indicate that micrometastasis formation by Lewis lung carcinoma cells involves a sequence of events starting with rapid extravasation after arrest in the lung within 1 day, followed by death of most cells at 2-3 days and subsequent new growth and expansion of persisting tumor cells from 4 days postinjection.
authors.affiliation: Laboratory of Pathology, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: H
authors.initials: H
authors.lastname: Nakanishi
authors.forename: A
authors.initials: A
authors.lastname: Masuda
authors.forename: N
authors.initials: N
authors.lastname: Tezuka
authors.forename: M
authors.initials: M
authors.lastname: Mutai
authors.forename: M
authors.initials: M
authors.lastname: Tatematsu
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000473:pathology* / Q000556:secondary*; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D003094:Collagen / Q000032:analysis; D005798:Genes, Bacterial; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007763:Lac Operon; D008175:Lung Neoplasms / Q000473:pathology* / Q000556:secondary*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D009368:Neoplasm Transplantation; D009360:Neoplastic Cells, Circulating / Q000473:pathology
chemical_list: D003094:Collagen