In vitro culture of primary plasmacytomas requires stromal cell feeder layers.

Abstract

Attempts to grow primary murine plasmacytomas in vitro have, to date, been largely unsuccessful. In this study, we demonstrate that long-term in vitro growth of primary plasmacytomas is accomplished by using feeder layers composed of stromal cells from the initial site of plasmacytomagenesis. The early neoplastic lines established in this manner are dependent on physical contact with the stromal layer, which is mediated in part by CD44, for growth and survival. The stromal cells provide at least two stimuli for the plasma ceUls, one being interleukin 6 and the second, of unknown nature, resulting from direct physical interaction that cannot be replaced by soluble factors. These plasma cell lines have been passaged for as long as 20 months yet still maintain characteristics associated with primary plasmacytomas as they will grow in vivo only in pristane-primed animals, indicating a continued dependence on the pristane-induced microenvironment characteristic of early-stage tumors. The ability to grow primary plasmaicytomas in culture and maintain their "primary" properties provides a model system for detailed analysis of early events in plasma cell tumor progression involving neoplastic cells completely dependent on physical contact with a stromal feeder layer for survival and expansion.

Anti-CD47 antibodies promote phagocytosis and inhibit the growth of human myeloma cells

“…12,33 The bone marrow microenvironment is critical for myeloma cell survival and proliferation. [34][35][36][37] In addition, the bone marrow microenvironment has been reported to protect myeloma cells from chemotherapy. 38,39 We have shown that patient myeloma cell growth is dependent on human bone marrow microenvironment.…”

Organ involvement and phenotypic adhesion profile of 5T2 and 5T33 myeloma cells in the C57BL/KaLwRij mouse

“…Preliminary experiments could demonstrate some growth of 5T2 MM in vitro when co-cultured with a stromal cell layer (consisting of bone marrow fibroblasts) (unpublished data). In contrast, 5T33 MM cells grow in a stroma-independent fashion (Degrassi et al, 1993).…”

“…Degrassi (1993) demonstrated that the interaction of CD44 with its ligand hyaluronate was responsible for part of the adhesion of plasmacytomas on stromal cell layers.…”

“…Most artificial animal models use human MM cell lines injected into severe combined immunodeficient (SCID) mice Alsina et al, 1995), chemically induced mouse plasmacytomas (Degrassi et al, 1993) or genetically modified hybridomas (Okada et al, 1995). As in human MM, it is expected that the interactions of mouse MM cells with the stromal cells and osteoclasts are based on a complex network of cytokines and adhesion molecules, inducing a paracrine proliferation of MM.…”

Lymph nodes and Peyer's patches of IL-6 transgenic BALB/c mice harbor T(12;15) translocated plasma cells that contain illegitimate exchanges between the immunoglobulin heavy-chain μ locus and c-myc

“…23 The apparent promotion of 5Ј-C /c-myc + clones in IL-6 transgenic BALB/c mice can be added to the body of evidence on the significance of IL-6 for plasmacytomagenesis in conventional BALB/c mice. [24][25][26] Furthermore, the finding that BALB/c mice homozygous for an IL-6-null allele (BALB/c.IL-6 −/− ) were completely resistant to plasmacytomagenesis induced by the pristane 27 and the Myc and Raf expressing retrovirus, J3V1, 28 established that IL-6 plays a unique and requisite role in both inflammation-induced and virally induced plasmacytoma development. Subsequent studies with another retrovirus that constitutively co-expressed Abl and Myc revealed an important mechanism by which IL-6 facilitates plasmacytomagenesis, the cooperation with Myc.…”