Distinct lung-colonizing and lung-metastasizing cell populations in B16 mouse melanoma

Summary In vitro cloned lines derived from a primary nickel-induced rat rhabdomyosarcoma exhibited diverse levels of susceptibility to spontaneous NK activity. The presence of NK target structures was revealed by competition assays on all cloned cell lines, and the NK susceptibility of the tumour lines varied according to their osmotic fragility. Tumour cell lines derived from metastatic lung nodules presented similar NK susceptibilities to cells originating from the primary tumour. However, cloned cell lines differed in their capacity to form lung colonies after i.v. injection, and in their potential for invading lungs after s.c. primary tumour development. No correlation was found between lung colonization potential and NK resistance. Studies of the correlation between metastatic potential and NK sensitivity revealed that (1) all the NK resistant tumour cells were highly metastatic; (2) NK susceptible tumour cells could be either highly or weakly metastatic. Therefore, highly metastatic tumour cells could be either resistant or susceptible to NK lysis. We conclude that the property of resistance to NK contributes to a high metastatic potential. However, other properties could counterbalance and finally prevail over NK susceptibility thus enabling NK susceptible cell lines to be also highly metastatic.

Section: Discussionsupporting

confidence: 72%

Variable susceptibility to NK activity of cloned cell lines derived from a primary rat rhabdomyosarcoma: Relationship to metastatic potential

Poupon¹,

Judde²,

Pot-Deprun³

et al. 1983

“…This assay correlates with metastasis in some systems (Talmadge & Fidler, 1982) but not in others (Stackpole, 1981). Both 1G8 and 1G3 cells colonized the lungs although the loose 1G3 cells produced greater pulmonary and extrapulmonary growth.…”

Section: Aggregation and Disaggregation The Results Inmentioning

confidence: 85%

Morphological and metastatic murine melanoma variants: motility, adhesiveness, cell surface and in vivo properties

Clark¹,

Js²,

Sidebottom³

1987

The results show enhanced differences in metastatic potential of tight and loose clones after selective cloning and that there may be important differences in motility and cell-substrate interactions. Foulds (1949) introduced the term tumour progression to describe the process by which some tumours become more malignant during their growth. Nowell (1976) attributed this to genetic instability, although genetic or epigenetic processes could result in the emergence of variant cells with growth advantages which differ from the main population in the expression of specific characters (Frost & Kerbel, 1983;Schimke et al., 1985).The existence within tumours of cells heterogeneous for the expression of a wide range of in vivo and in vitro characters is well documented (for reviews see Heppner, 1984;Nicolson, 1984).We have previously reported heterogeneity of clonal morphology in a metastatic melanomaxlymphocyte hybrid tumour cell line (Clark & Sidebottom, 1984). These variants grow either as tight or loose colonies and the isolation of cell lines, stable for clonal morphology, which have low or high metastatic phenotypes has been described (Clark & Sidebottom, 1984). The morphology and patterns of growth of these variants suggests a number of ways in which these cells may differ and which might account for their behavioural differences in vitro. These include intercellular and cell-substrate adhesion and motility, which in turn are dependent upon cell surface properties. Various stages of the metastatic cascade, for example local invasion or tumourcapillary endothelium adhesion are partially dependent upon intercellular and cell-substrate adhesion and motility (Weiss, 1980;Varani et al., 1980;Nicolson et al., 1986). The cell surface has an important role in these interactions and has been extensively studied for correlations with metastasis and organ colonization (Turner, 1982;Nicolson, 1984).Observation and measurement of adhesion and motility in vivo have inherent difficulties, but these characters can be investigated in vitro and some clues about their possible significance in vivo thereby gained (Briles & Kornfeld, 1978; Hart, 1979;Vollmers & Birchmeier, 1983;McCarthy et al., 1985).We have, therefore, looked at the adhesive and motile properties of tight and loose cells and also examined their cell surfaces by lectin binding to PAGE separated glycoproteins, radio-iodination of proteins and quantitation of sialic acid content. (Sidebottom & Clark, 1983). The cell lines 1G8(6F) and 1G3(4E) were selected from F87.CI.6T2 cells for tight or loose clonal morphology respectively and their in vitro and in vivo properties have been described elsewhere (Clark & Sidebottom, 1984). Cells were maintained in MEM +10% newborn calf serum (Flow) (cMEM) and subcultured when confluent; they were regularly tested for mycoplasma and found to be negative. Wiscm cells were derived from explanted hearts from one day old Wistar rats and were maintained in DMEM + 10% foetal calf serum (Gibco) +10% tryptose phosphate broth (Difco). To prod...

“…Received 30 October 1982;accepted 12 December 1982 now more usually referred to as "colonization potential." It has been shown that cells with a high colonization potential are not necessarily efficient at establishing spontaneous metastases after s.c. injection (Stackpole, 1981;Weiss et al, 1982).…”

mentioning

confidence: 99%

Cell fusion segregates progressive growth from metastasis

Sidebottom¹,

Clark²

1983

Summary Cell fusion has been used to analyse the genetic determinants of metastasis at the cellular level. Highly metastatic mouse melanoma cells were fused with diploid mouse lymphocytes and a range of hybrid clones isolated and tested for tumorigenicity and metastatic potential by s.c. injection into newborn, histocompatible, sublethally-irradiated mice. Although almost all clones tested were tumorigenic, most had considerably reduced metastatic potential. This suggests that tumorigenicity and metastasis are determined by different genetic elements. Histological examination of primary tumours produced by metastatic and nonmetastatic hybrid cell lines showed that an essential step in the production of metastases is the separation of tumour cells from the main tumour mass and their movement into the surrounding tissues. The primary tumours of a metastatic hybrid cell line showed local invasiveness whereas those of a non-metastatic cell line did not.