Tumor-derived interleukin-8 stimulates osteolysis independent of the receptor activator of nuclear factor-κB ligand pathway

Manali S. Bendre, Aaron G. Margulies, Brandon Walser, Nisreen S. Akel, Sudeepa Bhattacharrya, Robert A. Skinner, Frances Swain, Vishnu Ramani, Khalid Mohammad, Lisa L. Wessner, Alfredo Martinez, Theresa Guise, John Chirgwin, Dana Gaddy, Larry J. Suva

Research output: Contribution to journalArticle

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Abstract

Bone is a common site of cancer metastasis. Breast, prostate, and lung cancers show a predilection to metastasize to bone. Recently, we reported that the chemokine interleukin 8 (IL-8) stimulates both human osteoclast formation and bone resorption. IL-8 mRNA expression was surveyed in a panel of human breast cancer lines MDA-MET, MDA-MB-231, MDA-MB-435, MCF-7, T47D, and ZR-75, and the human lung adenocarcinoma cell line A549. IL-8 mRNA expression was higher in cell lines with higher osteolytic potential in vivo. Human osteoclast formation was increased by MDA-MET or A549 cell-conditioned medium, but not by MDA-MB-231. Pharmacologic doses of receptor activator of nuclear factor-κB (RANK)-Fc or osteoprotogerin had no effect on the pro-osteoclastogenic activity of the conditioned medium; however, osteoclast formation stimulated by conditioned medium was inhibited 60% by an IL-8-specific neutralizing antibody. The data support a model in which tumor cells cause osteolytic bone destruction independently of the RANK ligand (RANKL) pathway. Tumor-produced IL-8 is a major contributor to this process. The role of secreted IL-8 isoforms was examined by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, which detected distinct IL-8 isoforms secreted by MDA-MET and MDA-231 cells, suggesting different pro-osteoclastogenic activities of the two IL-8-derived peptides. These data indicate that (a) osteoclast formation induced by MDA-MET breast cancer cells and A549 adenocarcinoma cells is primarily mediated by IL-8, (b) cell-specific isoforms of IL-8 with distinct osteoclastogenic activities are produced by tumor cells, and (c) tumor cells that support osteoclast formation independent of RANKL secrete other pro-osteoclastogenic factors in addition to IL-8.

Original languageEnglish (US)
Pages (from-to)11001-11009
Number of pages9
JournalCancer Research
Volume65
Issue number23
DOIs
StatePublished - Dec 1 2005
Externally publishedYes

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Osteolysis
Cytoplasmic and Nuclear Receptors
Interleukin-8
Ligands
Osteoclasts
Neoplasms
Conditioned Culture Medium
RANK Ligand
Protein Isoforms
Breast Neoplasms
Bone and Bones
Messenger RNA
Bone Resorption
Neutralizing Antibodies
Chemokines
Lung Neoplasms
Mass Spectrometry
Prostatic Neoplasms
Adenocarcinoma
Lasers

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Bendre, M. S., Margulies, A. G., Walser, B., Akel, N. S., Bhattacharrya, S., Skinner, R. A., ... Suva, L. J. (2005). Tumor-derived interleukin-8 stimulates osteolysis independent of the receptor activator of nuclear factor-κB ligand pathway. Cancer Research, 65(23), 11001-11009. https://doi.org/10.1158/0008-5472.CAN-05-2630

Tumor-derived interleukin-8 stimulates osteolysis independent of the receptor activator of nuclear factor-κB ligand pathway. / Bendre, Manali S.; Margulies, Aaron G.; Walser, Brandon; Akel, Nisreen S.; Bhattacharrya, Sudeepa; Skinner, Robert A.; Swain, Frances; Ramani, Vishnu; Mohammad, Khalid; Wessner, Lisa L.; Martinez, Alfredo; Guise, Theresa; Chirgwin, John; Gaddy, Dana; Suva, Larry J.

In: Cancer Research, Vol. 65, No. 23, 01.12.2005, p. 11001-11009.

Research output: Contribution to journalArticle

Bendre, MS, Margulies, AG, Walser, B, Akel, NS, Bhattacharrya, S, Skinner, RA, Swain, F, Ramani, V, Mohammad, K, Wessner, LL, Martinez, A, Guise, T, Chirgwin, J, Gaddy, D & Suva, LJ 2005, 'Tumor-derived interleukin-8 stimulates osteolysis independent of the receptor activator of nuclear factor-κB ligand pathway', Cancer Research, vol. 65, no. 23, pp. 11001-11009. https://doi.org/10.1158/0008-5472.CAN-05-2630
Bendre, Manali S. ; Margulies, Aaron G. ; Walser, Brandon ; Akel, Nisreen S. ; Bhattacharrya, Sudeepa ; Skinner, Robert A. ; Swain, Frances ; Ramani, Vishnu ; Mohammad, Khalid ; Wessner, Lisa L. ; Martinez, Alfredo ; Guise, Theresa ; Chirgwin, John ; Gaddy, Dana ; Suva, Larry J. / Tumor-derived interleukin-8 stimulates osteolysis independent of the receptor activator of nuclear factor-κB ligand pathway. In: Cancer Research. 2005 ; Vol. 65, No. 23. pp. 11001-11009.
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AU - Akel, Nisreen S.

AU - Bhattacharrya, Sudeepa

AU - Skinner, Robert A.

AU - Swain, Frances

AU - Ramani, Vishnu

AU - Mohammad, Khalid

AU - Wessner, Lisa L.

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