Endothelial cells in the bone marrow of patients with multiple myeloma.
Endothelial cells (EC) were extracted through a lectin-based method from bone marrow of 57 patients with active multiple myeloma (MM) and compared with their healthy quiescent counterpart, human umbilical vein EC (HUVEC). MMECs exhibit specific antigens that indicate ongoing angiogenesis and embryo vasculogenesis; solid intercellular connections, hence stability of MM neovessels; and frequent interactions with plasma cells, hence tumor dissemination. They show heterogeneous antigen expression, hence existence of subsets. Their main genetic markers are indicative of a vascular phase. They show intrinsic angiogenic ability, because they rapidly form a capillary network in vitro, and extrinsic ability, because they generate numerous new vessels in vivo. They vividly secrete growth and invasive factors for plasma cells. They signal through kinases mandatory for development of neovascularization. Ultrastructurally, they are abnormal and show metabolic activation, like tumor ECs. Thalidomide heavily interferes with their functions. Vasculogenesis and angiogenesis might contribute to the MM vascular tree and progression, in the form of growth, invasion, and dissemination. In view of the heterogeneity of the antigenic phenotype of MMECs, a mixture (or a sequence) of antiangiogenic agents coupled with thalidomide would seem plausible for the biologic management of MM.
Vacca
Angelo
A
Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Policlinico-Piazza Giulio Cesare, 11, I-70124 Bari, Italy. a.vacca@dimo.uniba.it
Ria
Roberto
R
Semeraro
Fabrizio
F
Merchionne
Francesca
F
Coluccia
Mauro
M
Boccarelli
Angela
A
Scavelli
Claudio
C
Nico
Beatrice
B
Gernone
Angela
A
Battelli
Feliciana
F
Tabilio
Antonio
A
Guidolin
Diego
D
Petrucci
Maria Teresa
MT
Ribatti
Domenico
D
Dammacco
Franco
F
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D001853:Bone Marrow / Q000098:blood supply / Q000473:pathology*; D002196:Capillaries / Q000187:drug effects / Q000254:growth & development; D016022:Case-Control Studies; D002469:Cell Separation; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000098:blood supply / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D013792:Thalidomide / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology
D015415:Biomarkers; D013792:Thalidomide