Sporadic somatic fusion between MDAY-D2 murine tumor cells and DBA/2 host cells: Role in metastasis

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Abstract
An ouabain- and 6-thioguanine-resistant mutant (K3T103) of the metastatic MDAY-D2 murine tumor cell line was transplanted s.c. into syngeneic DBA/2 mice in order to isolate K3T103 x host cell hybrids emerging in vivo, and examine their metastatic potential. Of 10 tumor-bearing animals that were analyzed at various time intervals, only 3 developed fusion products in the primary site, present at a frequency ranging between 10−5 and 10−4. These hybrids survived in HAT + ouabain medium, had a lymphoblastoid morphology and a hypo-tetraploid karyotype, were non-adherent, and were as rapidly metastatic as K3T103 cells when transplanted s.c. or i.v. into DBA/2 mice. All these characteristics were shared by cloned hybrids generated in vitro following polyethylene glycol (PEG)-mediated fusion of K3T103 cells with normal DBA/2 normal splenocytes. In marked contrast, the products of K3T103 x DBA/2 normal lung fibroblast fusion displayed a fibroblastic appearance, were adherent, progressively ceased to divide and remained dormant for several weeks in culture. These results indicate: (1) that spontaneous fusion of K3T103 cells with host cells in the course of their expansion and subsequent dissemination is a stochastic and rare event, and (2) that since the expression of their tumorigenic and metastatic potential is retained after fusion with splenocytes, host cells of lymphoreticular origin are most likely involved in that process.