A new experimental metastasis model in athymic nude mice, the human malignant melanoma lox

Abstract

The human tumor line LOX was established as an s.c. xenograft in nude mice from a lymph-node metastasis of a patient with malignant melanoma. I.v. injection into adult nude mice of single-cell suspensions prepared from xenografts resulted in progressively growing lung tumor colonies that killed the animals. No difference in colony formation was seen between cells taken from lung colonies and s.c. xenografts. An in vitro cell line, LOX-L, was established from lung colonies, and the monolayer cells, detached with EDTA, retained the same ability to form experimental lung metastases. In a total of 14 experiments, 82 of 89 mice receiving 1 X 10(6) viable tumor cells died with a mean survival time of 34.1 +/- 4.8 days. Long-term passaging in vivo and in vitro did not result in any alteration of the lung-colonizing potential of the LOX cells, whereas trypsinization of the cells before i.v. injection reduced lung colony formation. The life span was inversely related to the number of LOX cells injected, permitting estimation of the cell kill caused by chemotherapy. Mice injected i.v. with the LOX cells showed the same relative response to cis-diamminedichloroplatinum (CDDP) and mitozolomide (MZA) as did animals carrying s.c. xenografts. The LOX cells have shown a remarkable stability and similarity to the cells of the patient's tumor with respect to morphology, karyotype and chemosensitivity. The LOX model may be useful for testing effects of therapy on lung micro- and macrometastases, and the activity of antimetastatic agents, as well as for studying mechanisms involved in the metastatic process.

Sensitive PCR method for the detection and real-time quantification of human cells in xenotransplantation systems

“…This problem for instance arises when metastasising models of human solid tumours are used (Giavazzi et al, 1986;Fodstad et al, 1988;Morikawa et al, 1988;Shoemaker et al, 1991) and their growth and dissemination potential has to be evaluated for an estimation of efficacy of therapeutic approaches.…”

Helix pomatia agglutinin binding in human tumour cell lines: correlation with pulmonary metastases in nude mice

“…in nude mice. The LOX cell line gives lung colonies (Fodstad et al, 1988b), while the FEMX-I cells give adrenal, subcutaneous and brown fat metastases (Fodstad et al, 1988a (Figure 2). The development of extrapulmonary metastases in mice showed no relationship to lectin receptor levels in any of the cell lines tested.…”

Effective Intravenous Therapy of Murine Pulmonary Metastases with an Oncolytic Herpes Virus Expressing Interleukin 12

“…Animals inoculated with SCC VII cells harvested with extended trypsinization developed fewer and smaller pulmonary nodules than those inoculated with an identical number of cells harvested with brief trypsinization. Trypsinization of tumor cell lines in vitro has previously been noted to affect tumorigenicity in vivo (16). We observed that extended trypsinization caused SCC VII cells to form a single cell suspension, whereas brief trypsinization left some SCC VII cells clustered together in small groups.…”