Multiple myeloma cell growth predominantly stimulated by bone-derived IGFs

07-06-2006

"Multiple myeloma (MM) is a fatal disease that affects plasma cells. Patients with MM have I or more osteolytic lesions in their bone tissues, where insulin-like growth factors (IGFs; IGF-I and IGF-II) are mainly stored.

"The role of bone-derived IGFs in the development of MM has not been extensively studied because reliable animal models are lacking," researchers in Japan report.

According to K. Araki and colleagues at Japan National Cancer Center in Chiba, "We established an animal model using a human MM cell line, RPMI8226, in nonobese diabetic/severe-combined immunodeficient (NOD/SCID) mice implanted with human adult bone (HAB) fragments.

"Treatment with an antihuman IGF-neutralizing monoclonal antibody, KM1468, inhibited the IGF-I-stimulated phosphorylation of type-I IGF receptors (IGF-IR) in RPM18226 cells and the activation of the downstream P13-K/Akt signaling pathway in vitro."

"KM1468 inhibited IGF-I-mediated RPM18226 cell growth in a dose-dependent manner. In the NOD/SCID-HAB model," continued investigators, "treatment with KM1468 significantly inhibited the growth of RPM18226 cells (p<0.02)."

"These results indicated that the growth of MM cells was predominantly stimulated not by serum-derived IGFs, but by bone-derived IGFs. Furthermore," concluded Araki, "the targeting of bone-derived IGFs, using a neutralizing antibody, may offer a new therapeutic strategy for MM."

Araki and colleagues published their study in International Journal of Cancer (Inhibition of bone-derived insulin-like growth factors toy a ligand-specific antibody suppresses the growth of human multiple myeloma in the human adult bone explanted in NOD/SCID mouse. Int J Cancer, 2006;118(10):2602-2608).

For additional information, contact A. Ochiai, National Cancer Center, Institute Research, Division Pathology, E 6-5-1 Kashiwanoha, Kashiwa, Chiba 2778577, Japan.

Publisher contact information for the International Journal of Cancer is: Wiley-Liss, Division John Wiley & Sons Inc., 111 River St., Hoboken, NJ 07030, USA.

Keywords: Chiba, Japan, Neutralizing Monoclonal Antibody, Insulin-Like Growth Factors, Multiple Myeloma, Therapeutic Strategy, NOD/CSID Mice.

This article was prepared by Cancer Gene Therapy Week editors from staff and other reports. Copyright 2006, Cancer Gene Therapy Week via NewsRx.com.