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

Abstract

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.

Acquired resistance towards immune defense during metastatic progression represents a secondary phenomenon

“…There are numerous reports showing that metastatic spread (spontaneous or artificial) is significantly influenced by the activation status of NK cells, i.e. increased incidence of metastases in NKideficient situations as in beige or young mice and after depletion of NK cells by anti-asialo GMI or estrogen treatment (Hanna, 1980;Talmadge et al, 1980;Hanna and Schneider, 1983;Saijo et al, 1984;Barlozzari et al, 1985), vs low incidence after activation of NK cells by biological response modifiers (Fidler, 1980;Stackpole, 1981;Hanna, 1982;Warner and Dennert, 1982;Poupon et al, 1983;Brunda et al, 1984. Yamamura et al, 1984, or after transplantation of NK cells and NK clones (Hanna and Burton, 1981;Warner and Dennert, 1982;Barlozzari et al, 1984).…”

“…Attempts to support the role of non-adaptive immunity in tumor surveillance by looking at the mirror image, i. e. correlation between adaptation to/resistance against NK cells and increased metastatic capacity, did not lead to similarly convergent results Poste et al, 1980;Stackpole, 1981;Starkey et al, 1982;Gorelik et al, 1982;Poupon et al, 1983;Brodt et al, 1983;Matzku, 1984). Resistance to non-specific immune defense via selection or adaptation was reported to result frequently, but not necessarily, in increased metastatic potential.…”