Laminin-332 (Laminin-5) is the major motility ligand for B cell chronic lymphocytic leukemia.
Cell adhesion and motility are central aspects in the pathophysiology of B cell chronic lymphocytic leukemia (B-CLL), but the role of specific extracellular matrix proteins is still to be completely unveiled. Purified peripheral blood neoplastic cells of B-CLL patients migrated poorly on laminins-111,-411,-511, but showed pronounced motility on laminin (LM)-332 in a high percentage of cases. B-CLL cell motility on LM-332 was mediated by the alpha3beta1 integrin and was preferentially observed in cells carrying a mutated IgV(H) gene profile. Within normal lymph nodes, LM-332 was circumscribed around blood vessels and to areas corresponding to marginal zones, where it was deposited in a pattern reminiscent of reticular fibers. Conversely, in B-CLL involved lymph nodes, a positive LM-332 reticular mesh was diffusely evident, throughout the disrupted nodal architecture. In the present study we identified LM-332 as a crucial motility-promoting factor for B-CLL lymphocytes and as a potential constituent favoring the dissemination of B-CLL lymphocytes through vascular basement membranes and possibly lymph node compartments.
Spessotto
Paola
P
Experimental Oncology 2, Centro di Riferimento Oncologico, IRCCS, Aviano (PN), Italy.
Zucchetto
Antonella
A
Degan
Massimo
M
Wasserman
Bruna
B
Danussi
Carla
C
Bomben
Riccardo
R
Perris
Roberto
R
Canzonieri
Vincenzo
V
Radillo
Oriano
O
Colombatti
Alfonso
A
Gattei
Valter
V
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007150:Immunohistochemistry; D039201:Integrin alpha3beta1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008198:Lymph Nodes / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000097794:Kalinin
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D005353:Fibronectins; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D039201:Integrin alpha3beta1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020033:Protein Isoforms; D012333:RNA, Messenger; D000097794:Kalinin