Expression of L-selectin and efficient binding to high endothelial venules do not modulate the dissemination potential of murine B-cell lymphoma.
The homing receptor L-selectin is essential for the migration of naive lymphocytes into peripheral lymph nodes. In contrast to naive lymphocytes, activated and memory cells down-regulate L-selectin and enter peripheral lymph nodes by an L-selectin-independent mechanism. In view of the concept that lymphomas present the malignant counterparts of normal lymphocytes at a defined stage of differentiation, it has been suggested that in contrast to lymphomas with a memory/activated cell phenotype, L-selectin is essential for dissemination of lymphomas that represent naive cells. 38C-13 is a murine B-cell lymphoma with an immature naive cell phenotype. 38C-13 cells express high levels of L-selectin and bind to lymph node high endothelial venules in an L-selectin-dependent manner. In this study we demonstrate that treatment of 38C-13 tumor-bearing mice with anti-L-selectin antibodies did not inhibit tumor dissemination to peripheral lymph nodes. Moreover, L-selectin-negative 38C-13 variant cells disseminated as efficiently as wild-type cells. Thus, in spite of its expression, L-selectin is not required and does not affect the metastatic potential of the tumor. L-selectin of the malignant cells and of normal lymphocytes appears to be functionally different. Thus, whereas antibody cross-linking of L-selectin resulted in down-modulation of the receptor in normal lymphocytes, cross-linking had no effect on L-selectin expression in 38C-13 cells, suggesting that, in spite of comparable levels of surface expression in normal and malignant cells, L-selectin may be functionally impaired in some malignant cells.
Aviram
R
R
Department of Human Microbiology, Sackler School of Medicine, Tel-Aviv University, Israel.
Raz
N
N
Kukulansky
T
T
Hollander
N
N
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D004730:Endothelium, Vascular / Q000378:metabolism*; D019041:L-Selectin / Q000032:analysis / Q000502:physiology*; D008207:Lymphatic Metastasis; D016393:Lymphoma, B-Cell / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008809:Mice, Inbred C3H
D000911:Antibodies, Monoclonal; D019041:L-Selectin