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CancerQuest > Introduction to Patient Information > Introduction to Cancer by Type > Multiple Myeloma: Introduction > Multiple Myeloma: Tumor Biology

Multiple Myeloma: Tumor Biology

The malignant B plasma cells in Multiple Myeloma generally migrate to the bone marrow. Once in, they attach to the supporting structures and cells (matrix). The matrix supports the cells as they proliferate. Within the bone marrow, numerous growth factors and other proteins influence the growth of the cells.⁽¹⁾

Some of the growth factors and cytokines that play a role in multiple myeloma are:

• Interleukin 6 (IL-6) - a cytokine secreted by T cells. Stimulates other white blood cells (leukocytes), including B cells.⁽²⁾
• Tumor Necrosis Factor alpha (TNFα) - a cytokine mainly secreted by macrophages. Stimulates the immune system and induces inflammation.
• Vascular Endothelial Growth Factor (VEGF) - a growth factor secreted by cells in the bone marrow. Promotes angiogenesis and therefore the growth of tumors.
• Insulin-like Growth Factor I (IGF-1) - a growth factor that activates the AKT pathway. Promotes growth and inhibits cell death.
• Stromal Derived Factor 1 alpha (SDF-1α) - a cytokine that regulates the migration of blood cells to the bone marrow.
• Hepatocyte Growth Factor (HGF) - a glycoprotein produced by cells in the bone marrow. Promotes adhesion of cells to the matrix and may regulate cell migration.⁽³⁾

Genes that have been implicated in multiple myeloma include:

• PTTG-1 - a proto-oncogene coding for a transcription factor associated with progression in multiple myeloma⁽⁴⁾
• PI3K - a gene that codes for a kinase which promotes cell division.⁽⁵⁾
• AKT - an proto-oncogene. The protein product inhibits cell death. ⁽⁵⁾
• GILZ - a tumor supressor gene which promotes cell death when activated by glucocorticoids. It is inhibited by the activities of PI3K and AKT. ⁽⁵⁾

Learn more about cancer genes

References for this page:

1. Hideshima T, Podar K, Chauhan D and KC Anderson. "Cytokines and signal transduction." (2005) Best Pract Res Clin Haematol. 18(4):509-24. [PUBMED]
2. Huston A and GD Roodman."Role of the microenvironment in multiple myeloma bone disease." (2006) Future Oncol. Jun;2(3):371-8 [PUBMED]
3. Holt RU, Fagerli UM, Baykov V, Ro TB, Hov H, Waage A, Sundan A, Borset M. "Hepatocyte growth factor promotes migration of human myeloma cells". Haematologica. 2008 Apr;93(4):619-22. [PUBMED]
4. Chiriva-Internati M, Ferraro R, Prabhakar M, Yu Y, Baggoni L, Moreno J, Gagliano N, Portinaro N, Jenkins MR, Frezza EE, Hardwicke F, D'Cunha N, Kast W, Cobos E. "The pituitary tumor transforming gene 1 (PTTG-1): an immunological target for multiple myeloma." J Transl Med. 2008 Apr 2;6:15. [PUBMED]
5. Grugan KD, Ma C, Singhal S, Krett NL, Rosen ST. "Dual regulation of glucocorticoid-induced leucine zipper (GILZ) by the glucocorticoid receptor and the PI3-kinase/AKT pathways in multiple myeloma." J Steroid Biochem Mol Biol. 2008 Jun;110(3-5):244-54. Epub 2008 Apr 20. [PUBMED]