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 that they are deficient in complex gangliosides. Here, we report that the highly metastatic clone 4 appears more sensitive to activated adherent leukocytes 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 lymphocytes. 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 gangliosides or Campylobacter jejuni LPS with GM1-like structure (LPS-like GM1) significantly decrease the hypersensitivity of clone 4 to AL. On the other hand, the cleaving with neuraminidase of more than 50% of the sialic residues bound to endogenous gangliosides in resistant M4Be cells significantly increases their sensitivity to AL. Thus, our highly metastatic cells appear both very sensitive to activated AL when they are deficient in complex gangliosides and resistant to AL when they are transiently exposed to exogenous 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 secondary tumours.
Laboratoire des macrophages, IFR 31 Inserm, CHU Rangueil, Toulouse, France. yanne.thomas@free.fr
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Thomas
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D000328:Adult; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000502:physiology; D016123:Campylobacter jejuni; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival; D004926:Escherichia coli; D005677:G(M1) Ganglioside / Q000737:chemistry / Q000494:pharmacology; D005732:Gangliosides / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008545:Melanoma; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D012016:Reference Values; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D005732:Gangliosides; D008070:Lipopolysaccharides; D005677:G(M1) Ganglioside