Insulin-like growth factor I is a growth and survival factor in human multiple myeloma cell lines

Abstract

Human multiple myeloma (MM) represents a highly aneuploid tumor as shown by cytogenetic studies. This may partly explain the heterogeneity with regard to growth factor requirements demonstrated among MM cells. We have previously reported the expression of insulin-like growth factor I (IGF-I) and IGF-I receptor (IGF-IR) mRNA in some MM cell lines. In this study we investigated the role of IGF-I as a growth and/or survival factor in three MM cell lines: LP-1, EJM, and Karpas 707. We report that all cell lines expressed IGF-I and IGF-IR mRNA and protein. LP-1 and Karpas 707, but not EJM, were stimulated to proliferation in a dose-dependent manner by exogenous IGF-I. An IGF-IR blocking antibody inhibited both the IGF-I-induced and spontaneous growth of LP-1, and Karpas 707, while the EJM cell line was unaffected by the addition of the antibody. In conclusion, our results show that IGF-I can act as a growth factor in human MM, and they suggest that an autocrine IGF-I loop may contribute to the growth and survival in some MM cell lines.

Multiple myeloma cells are protected against dexamethasone‐induced apoptosis by insulin‐like growth factors

“…These studies demonstrate an increased expression of IGF and insulin receptors as B cells mature from the lymphoblastoid stage to plasma IGF Protection of Myeloma Cells from Apoptosis ᭧ 1997 Blackwell Science Ltd, British Journal of Haematology 97: [429][430][431][432][433][434][435][436][437][438][439][440] cells (Freund et al, 1993(Freund et al, , 1994 and an increased development of IGF-associated signal transduction pathways (Freund et al, 1994). In addition, IGFs and insulin can stimulate proliferation of plasma cells under some conditions (Kimata & Yoshida, 1994;Georgii-Hemming et al, 1996) and the current study documents their ability to promote survival of plasma cells. Finally it may be important that IGF-I is produced by osteoblasts (Canalis et al, 1988;Ernst & Froesch, 1988) and bone marrow stromal cells (Landreth et al, 1992).…”

“…Previous studies indicate that functional IGF receptors are expressed by plasma cells. Several myeloma cell lines as well as in vitro generated plasma cells express IGF-I, IGF-II and insulin receptors (Kimata & Yoshida, 1994;Georgii-Hemming et al, 1996). In a separate study, 8226 and U266 myeloma cell lines also expressed IGF-I and insulin receptors (Freund et al, 1993).…”

“…Cell line models suggest that as maturation increases within the B-cell lineage, expression of IGF-IRs and insulin receptors as well as functional IGF-related signal transduction pathways also increase (Freund et al, 1993(Freund et al, , 1994. Under some circumstances, IGF-I can stimulate proliferation of myeloma plasma cells (Freund et al, 1994;Kimata & Yoshida, 1994;Georgii-Hemming et al, 1996).…”

β2‐microglobulin as a negative growth regulator of myeloma cells

“…Here we report an unexpected finding that b 2 m induced apoptosis in primary myeloma cells from the majority of patients tested and in most myeloma cell lines in a concentration and time-dependent fashion, which was, however, counteracted by interleukin 6 (IL-6). We speculate that in myeloma patients, the tumour cells escape the apoptotic effects of b2m, probably through protection by cytokines with reported anti-apoptotic activity in myeloma (Kawano et al, 1988;Harding et al, 1994;Georgii-Hemming et al, 1996) or through interactions with the bone marrow microenvironment (Grigorieva et al, 1998).…”

Single‐cell RNA sequencing reveals chemokine self‐feeding of myeloma cells promotes extramedullary metastasis

“…Transcriptional factors specific for myeloma cells, such as IRF4, Blimp-1 (PRDM1), and XBP1, are also transcribed in BMMCs [26][27][28][29]. Upregulation of nourishing growth factors for myeloma, such as HGF, IGF1, and VEGF [30][31][32][33], was also confirmed. Furthermore, tumorigenic genes correlated with PC1 [34][35][36][37][38][39] (Fig.…”