Tumorigenic potential and disease manifestations of malignant B-cell variants differing in their fibronectin adhesiveness.
OBJECTIVE
Microenvironmental interactions of malignant B cells can modulate various in vitro physiological responses, including proliferation, migration, apoptosis, and drug resistance. Disease manifestations of human malignant B-cell variants, isolated based on their differential interactions with fibronectin, were examined in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice.


METHODS
Disease manifestations were assessed by pathological examinations and skeletal imaging of NOD/SCID mice injected with malignant B-cell variants. Dissemination patterns were analyzed by whole-body real-time imaging of mice injected with fluorescence-labeled malignant cells.


RESULTS
Initial dissemination patterns and dynamics of both high (type A) and low (type F)-adherent variants, following intravenous inoculation, were similar. Both cell types reached the spleen and liver within 30 minutes after injection, then increasingly accumulated within the bone marrow. Mice injected with type-A cells developed multiple myeloma-like disease within the bone marrow, with multiple lytic bone lesions. In contrast, type-F cells displayed low tumorigenic capacity in spite of their efficient homing to the bone marrow niche. In addition, type-A cells grew as extramedullary tumors in some of the intravenous-inoculated mice, and formed solid tumors following subcutaneous injection. Both cell variants retained their characteristics surface markers following in vivo outgrowth as tumors, indicating that at least some of their properties are relatively stable.


CONCLUSIONS
Data suggest that the differential tumorigenicity of B-cell adhesive variants is attributable to the capacity of type-A cells to survive and proliferate within the bone marrow, rather than to different initial dissemination of the two cell populations.
Nadav
Liat
L
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Kalchenko
Vyacheslav
V
Barak
Meir Max
MM
Naparstek
Elizabeth
E
Geiger
Benjamin
B
Katz
Ben-Zion
BZ
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002448:Cell Adhesion; D005353:Fibronectins / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000209:etiology* / Q000473:pathology; D009374:Neoplasms, Experimental / Q000209:etiology* / Q000473:pathology; D010014:Osteolysis; D055114:X-Ray Microtomography
D005353:Fibronectins