Influence of implantation site on formation of metastases

Meyvisch, C

doi:10.1007/bf00048482

Cited by 53 publications

(30 citation statements)

References 38 publications

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“…M04 1-4 cells were derived from the virally transformed murine M04 fibroblast cells upon transfection with a cDNA of human PLAP (type 2). The tumour incidence (100%), latency times, and tumour growth curves found for transfected M04 1-4 cells were similar to results obtained for nontransfected M04 cells which have been documented previously (Mareel et al, 1975;Meyvisch & Mareel, 1982). Our detailed characterisation of the PLAP synthesised by the M04 1-4 cells confirmed that all enzymatic and immunologic properties were conserved, and that it was localised on the outer surface of the plasma membrane of these M04 1-4 cells, making it an ideal target for tumour localisation and imaging.…”

Section: Discussionsupporting

confidence: 89%

Radiolocalisation and imaging of stably HPLAP-transfected MO4 tumours with monoclonal antibodies and fragments

Hendrix

Dauwe²,

Voorde³

et al. 1991

Br J Cancer

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Immunotargeting of PLAP-expressing tumours was studied for two radioiodinated, highly specific anti-PLAP monoclonal antibodies, 7E8 and 17E3, differing 10-fold in affinity, as well as for 7E8 F(ab')2 fragments. An anti-CEA monoclonal antibody or anti-CD3 F(ab')2 fragments were used as controls. Specific and non-specific targeting was examined in nude mice simultaneously grafted with PLAP-positive tumours derived from MO4 1-4 cells, and CEA-positive tumours, derived from 5583-S cells. Results indicated that (1) MO4 1-4 tumours, with a stable expression of PLAP on the plasma membrane, represent a useful new in vivo model for immunodirected tumour targeting; (2) differences in antibody affinity for PLAP in vitro are not reflected in antibody avidity for tumour cells in vivo; and (3) excellent selective and specific localisation of the PLAP-positive tumours is achieved when 7E8 F(ab')2 fragments are used. The high tumour/blood ratios (10.7 +/- 3.9 at 46 h after injection) were due to a much faster blood clearance of 7E8 F(ab')2 fragments. At this time point, the mean tumour/non-tumour tissue ratio was as high as 34.5, and the mean specific localisation index was 29.0. As expected, the F(ab')2 fragments provided high tumour imaging efficiency on gamma camera recording. These data imply important potentials of the PLAP/anti-PLAP system for immunolocalisation and therapy in patients, but also emphasise that in vitro criteria alone are not reflected in in vivo tumour localisation capacities of antibodies. Images Figure 1 Figure 3 Figure 4

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Section: Discussionsupporting

confidence: 89%

Radiolocalisation and imaging of stably HPLAP-transfected MO4 tumours with monoclonal antibodies and fragments

Hendrix

Dauwe²,

Voorde³

et al. 1991

Br J Cancer

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“…The fact that s.c. injection of Rama 950 feeders with Rama 900 cells produces a shorter time before the rats become moribund, and hence a possible increase in the rate of metastasis, suggests that such mesothelial cells may also exert a 'feeder' effect at this site, but not at the other two sites in vivo. Variation of metastatic potential with site of implantation has also been observed in other systems (Meyvisch, 1983;Unemori et al, 1984).…”

mentioning

confidence: 73%

“…Moreover, when Rama 900 cells were collected from the ascites of rats originally injected with Rama 900-12 cells and then passaged four times in culture before being reinjected s.c. into the mammary fat pad of fresh intact rats, the original incidence of tumours and metastases was not altered (not shown). This result eliminated the possibility that passage through syngeneic animals and subsequent culture caused changes in cellular behaviour in vivo (Meyvisch, 1983).…”

Section: Morphology Of Cultured Cellsmentioning

confidence: 99%

Isolation and properties of cell lines from the metastasising rat mammary tumour SMT-2A

Dj²,

Kim³

et al. 1989

Br J Cancer

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“…When primary tumor burden was relieved (ftpd. route) (11,19), thereby increasing the life span of the animal, "pea"-size lung tumor nodules were observed (Fig. 1).…”

Section: Methodsmentioning

confidence: 96%

Amplification and rearrangement of the Kirsten ras oncogene in virus-transformed BALB/c 3T3 cells during malignant tumor progression.

Radinsky¹,

Kraemer²,

Raines³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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Analyses of the cellular and viral Kirsten ras genes (c-Ki-ras and v-Ki-ras, respectively) Ki-ras led to no further rearrangements in the lung microfoci tumors isolated >40 days after injection. These data suggest (i) the significance of amplification and elevated expression of v-Ki-ras in tumor formation, (ii) correlation of this ampliflication with more effective tumor progression, and (iii) the selective advantage that cells with Ki-ras DNA sequence additions have in the formation of overt lung tumors.During tumor progression many changes may occur genotypically (1) and phenotypically (2), including increases in gene dosage and expression of oncogenes (3). The ras oncogene has special importance in select tumors. Harvey and Kirsten ras oncogenes were discovered as the transforming component of murine sarcoma retroviruses (4, 5), and N-ras was found in human DNA (3). DNA transfection experiments and isolation ofras genes from numerous tumors established that activation ofthe cellular ras protooncogene's transforming and tumorigenic potential occurs either by a point mutation replacing amino acids at position 12 or 61 in the encoded 21-kDa membrane protein (6) or by increasing the amount of the ras gene and hence its product (7). ras oncogenes can enhance transformation and tumorigenicity in established cell lines, but in primary cells a second oncogene is required with some exceptions (8).Although ras has been analyzed in primary tumor cells, much less is known about its state in metastatic populations. ras is of particular interest because of recent evidence pointing to its involvement in malignant tumor progression.Transfection with tumor DNA (9, 10) or activated ras oncogenes (11-13) demonstrated that the metastatic phenotype can be transferred between cells (14). ras DNA and RNA levels in NIH 3T3 transfectants and N-nitroso-Nmethylurea-induced tumors containing an activated cellular Harvey ras protooncogene (c-Ha-ras) showed gene amplification and increased expression in primary tumors with comparable levels in the metastatic lesions (14). These data suggest a role for ras in malignant tumor progression.These data prompted analyses of the Kirsten ras oncogene during tumor progression using a Kirsten murine sarcoma virus (KiMSV)-transformed BALB/p 3T3 cell line that harbors a replication-defective viral Kirsten ras oncogene (vKi-ras)-containing provirus (15). Cells were injected into athymic nude mice in four anatomical locations. The resulting primary tumors and lung metastases were isolated, adapted to in vitro growth, and analyzed for DNA levels and expression of v-Ki-ras and the cellular Kirsten ras protooncogene (c-Ki-ras) relative to the untransformed BALB/c 3T3 and KiMSV (parental) transformed cells. Analyses of lung metastases undergoing a second round of in vivo selection using specific tumor populations from the first round of injections were also performed. MATERIALS AND METHODSCells and Tumors. BALB/c 3T3 cells (clone A31) and KiMSV-transformed BALB/c 3T3 cells (nonproducer clone k-234...

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Influence of implantation site on formation of metastases

Cited by 53 publications

References 38 publications

Radiolocalisation and imaging of stably HPLAP-transfected MO4 tumours with monoclonal antibodies and fragments

Radiolocalisation and imaging of stably HPLAP-transfected MO4 tumours with monoclonal antibodies and fragments

Isolation and properties of cell lines from the metastasising rat mammary tumour SMT-2A

Amplification and rearrangement of the Kirsten ras oncogene in virus-transformed BALB/c 3T3 cells during malignant tumor progression.

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