Influence of gangliosides or LPS-like gangliosides on the tumoricidal activity of adherent leukocytes

We previously showed that highly metastatic clones derived from the poorly metastatic human melanoma cell line M4Be are very radiosensitive provided t hat they are deficient in complex gangliosides. Here, we report that the hi ghly metastatic clone 4 appears more sensitive to activated adherent leukoc ytes than M4Be via a transmembrane TNF-alpha -dependent mechanism. Adherent leukocytes (AL) were freshly isolated from different blood donors and were activated with Esherichia coli lipopolysaccharide (LPS). These AL contain 80 % (73-93 %) monocytes, 15 % (6-20 %) B lymphocytes and 5 % (1-8 %) T lym phocytes. The tumour cell survival following contact with AL was estimated with a clonogenic assay where isolated tumour cells were plated for 14 days with AL. We show on the one hand that either exogenous bovine brain GM1 ga ngliosides or Campylobacter jejuni LPS with GM1-like structure (LPS-like GM 1) significantly decrease the hypersensitivity of clone 4 to AL. On the oth er hand, the cleaving with neuraminidase of more than 50 % of the sialic re sidues bound to endogenous gangliosides in resistant M4Be cells significant ly increases their sensitivity to AL. Thus, our highly metastatic cells app ear both very sensitive to activated AL when they are deficient in complex gangliosides and resistant to AL when they are transiently exposed to exoge nous gangliosides or LPS-like gangliosides. These in vitro data may reflect the paradoxidal behaviour of highly metastatic cells in vivo which appear both very sensitive to physiological stresses and able to survive to form s econdary tumours. (C) 2001 Academie des sciences/Editions scientifiques et medicales Elsevier SAS.