In vitro growth of human multiple myeloma: implications for biology and therapy.
In vitro data allow presentation of a plausible scenario for the in vivo growth, progression, and dissemination of human multiple myeloma (MM) that involves the interactions between the monoclonal B-cell clone and the bone marrow (BM) microenvironment. A large series of adhesion and extracellular matrix molecules allow trapping of circulating plasma cell precursors within the BM, and a battery of locally released cytokines promote their growth and final differentiation. Malignant B cells establish close contacts with BM stromal cells and release a host of cytokines that recruit and activate BM stromal cells and also T lymphocytes to produce other cytokines. All these cytokines might conceivably act in concert in a self-perpetuating mechanism of mutual help between malignant plasma cells and BM stromal cells to favor the progressive expansion of the malignant clone through a sort of an "avalanche effect." Also, most cytokines produced by malignant B cells, stromal cells, and activated T lymphocytes, including IL-1 beta, TNF-beta, M-CSF, IL-3, and IL-6, have osteoclast-activating properties, thus explaining why the expansion of the B-cell clone is matched by the activation and numeric increase of osteoclasts.
Caligaris-Cappio
F
F
Dipartimento di Scienze Biomediche e Oncologia Umana, Università di Torino, Italy.
Gregoretti
M G
MG
Ghia
P
P
Bergui
L
L
D001402:B-Lymphocytes / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D008854:Microscopy, Electron; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D010950:Plasma Cells / Q000473:pathology
D016207:Cytokines; D006133:Growth Substances