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Access through your institution Buy or subscribe Fibroblast growth factor receptor 3 (FGFR3) is a membrane-anchored receptor tyrosine kinase that transmits intercellular signals mediated by

a family of fibroblast growth factors (FGFs). In multiple myeloma (MM), 15% of patients markedly upregulate FGFR3 as a consequence of a t(4;14)(p16.3;q32) translocation.1 Ectopic expression

of FGFR3 enhances MM cell proliferation and survival, demonstrating the oncogenic potential of FGFR3.2 Although a small fraction of MM cases with t(4;14)(p16.3;q32) also harbor an activating

mutation in FGFR3,3 the majority upregulate wild-type FGFR3, thus depending on FGF ligand for FGFR3 activation. The human FGF family contains at least 22 members, but previous studies

addressing FGF expression in MM have largely focused on FGF2. Bisping _et al._4 found FGF2 to be both expressed and released by MM cells, but their results were challenged by Colla _et

al._,5 thus leaving the nature of the FGF ligand involved in activation of FGFR3 in MM unclear. Among the cell lines used here, the OPM2, KMS11, KMS18, H929 and LP1 cells are known to

possess t(4;14)(p16.3;q32) as well as upregulate FGFR3 (Figure 1c). We therefore asked whether FGF2 or 8 can be released by these cells lines and therefore can activate FGFR3 in an autocrine

manner. We cultivated OPM2, KMS11, KMS18, H929 and LP1 cells for 72 h and purified FGF2 and 8 from the conditioned media based on their affinity for heparin (for details, see Supplementary

Information). Figure 1d shows that only KMS11 and KMS18 cells release a detectable amount of FGF2 into the culture media. Although primarily nuclear, the HMW FGF2 isoforms were also released

by both cell lines, similar to hairy cell leukemia.7 Although the FGF2 binding to the extracellular matrix may account for low levels of FGF2 detected in the culture media (Figure 1d), a

more likely explanation is that elevated FGF2 found in the blood of MM patients originates from another cellular source than the malignant clone itself. In the media conditioned by H929

cells, the protein band of approximately 20 kDa was found (Figure 1d). This protein appears to be cross-reacting with the FGF2 antibody, as there was no FGF2 detected in the H929 cell

lysates and its migration does not correspond to the known FGF2 isoforms (18, 22, 22.5 and 24 kDa bands; Figure 1b and d). No FGF8 was found in the media conditioned by any of the tested

cell lines (not shown). This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 12 print

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local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * Chesi

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Article  CAS  PubMed  PubMed Central  Google Scholar  Download references ACKNOWLEDGEMENTS This work was supported by Multiple Myeloma Foundation and Yang Sheng Tang USA Company. AUTHOR

INFORMATION AUTHORS AND AFFILIATIONS * Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA P Krejci, P B Mekikian & W R Wilcox * Department of Pediatrics, UCLA

School of Medicine, Los Angeles, CA, USA W R Wilcox Authors * P Krejci View author publications You can also search for this author inPubMed Google Scholar * P B Mekikian View author

publications You can also search for this author inPubMed Google Scholar * W R Wilcox View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING

AUTHOR Correspondence to P Krejci. ADDITIONAL INFORMATION Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu) SUPPLEMENTARY INFORMATION

SUPPLEMENTARY INFORMATION (DOC 31 KB) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Krejci, P., Mekikian, P. & Wilcox, W. The fibroblast growth

factors in multiple myeloma. _Leukemia_ 20, 1165–1168 (2006). https://doi.org/10.1038/sj.leu.2404202 Download citation * Published: 06 April 2006 * Issue Date: 01 June 2006 * DOI:

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