Association between ICAM-1 expression and metastatic capacity of murine B-cell hybridomas.
We previously reported that a derivative of the interleukin-6 (IL-6)-dependent B9 B-cell hybridoma (B9/LPNU1L) constitutively expressing an interleukin-1 alpha (IL-1 alpha) gene introduced by retrovirus-mediated gene transfer preferentially metastasized to bone marrow following intravenous injection into unirradiated syngeneic BALB/c mice. B9/LPNU1L cells recovered from the femoral marrow of a recipient with hind limb paralysis (denoted B9/BM1) retained their IL-6-dependency yet displayed enhanced metastatic capacity during serial transplantation in vivo. In contrast, autonomously-growing B9 variants spontaneously arising in vitro or IL-6-independent B9 derivatives created by infection with recombinant IL-6 retroviruses rarely gave rise to experimental metastases in syngeneic BALB/c or nude mice. Examination of cell adhesion molecule profiles by immunofluorescence flow cytometry has revealed high levels of CD44, moderate levels of VLA-4 and low levels of LFA-1 on all B9-series cells. By comparison, ICAM-1 expression was significantly elevated on B9/BM1 cells, with independent isolates stably expressing about 4-fold higher levels which were paralleled by corresponding increases in the steady-state levels of ICAM-1 mRNA. L-Selectin was not expressed by any of the cell lines. Despite higher ICAM-1 levels, cell aggregation assays revealed that LFA-1-ICAM-1 adhesive interactions were not involved in the homotypic adhesion of B9/BM1 cells but rather that binding of CD44 to endogenously-synthesized hyaluronan was responsible. Furthermore, B9/BM1 cells expressing high levels of ICAM-1 were found to be less susceptible to cytolysis by natural killer (NK) cells than their weakly metastatic or nonmetastatic counterparts.
Hawley
R G
RG
Division of Cancer Research, Sunnybrook Health Science Centre, Toronto, Ontario, Canada.
Wang
M H
MH
Fong
A Z
AZ
Hawley
T S
TS
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000951:Antigens, Neoplasm / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D015152:Blotting, Northern; D001853:Bone Marrow / Q000473:pathology*; D001854:Bone Marrow Cells; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002449:Cell Aggregation / Q000276:immunology / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D005260:Female; D006183:H-2 Antigens / Q000502:physiology; D006825:Hybridomas / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D007111:Immunity, Cellular; D018799:Intercellular Adhesion Molecule-1; D007375:Interleukin-1 / Q000096:biosynthesis; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D016201:Receptors, Lymphocyte Homing / Q000276:immunology
D000906:Antibodies; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D007375:Interleukin-1; D012333:RNA, Messenger; D016201:Receptors, Lymphocyte Homing; D018799:Intercellular Adhesion Molecule-1