A blocking antibody to nerve growth factor attenuates skeletal pain induced by prostate tumor cells growing in bone

Prostate cancer is unique in that bone is often the only clinically detectable site of metastasis. Prostate tumors that have metastasized to bone frequently induce bone pain which can be difficult to fully control as it seems to be driven simultaneously by inflammatory, neuropathic, and tumorigenic...

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Published in:Cancer research (Chicago, Ill.) Ill.), 2005-10, Vol.65 (20), p.9426-9435
Main Authors: HALVORSON, Kyle G, KUBOTA, Kazufumi, SEVCIK, Molly A, LINDSAY, Theodore H, SOTILLO, Julio E, GHILARDI, Joseph R, ROSOL, Thomas J, BOUSTANY, Leila, SHELTON, David L, MANTYH, Patrick W
Format: Article
Language:English
Subjects:
Analgesics
Analgesics, Opioid - therapeutic use
Animals
Antibodies - pharmacology
Biological and medical sciences
Bone and Bones - innervation
Bone Neoplasms - complications
Bone Neoplasms - secondary
Bone Remodeling
Brain - metabolism
Cell Line, Tumor
Disease Progression
Dogs
Gynecology. Andrology. Obstetrics
Male
Male genital diseases
Medical sciences
Mice
Mice, Nude
Morphine - therapeutic use
Nephrology. Urinary tract diseases
Nerve Growth Factor - antagonists & inhibitors
Nerve Growth Factor - genetics
Nerve Growth Factor - immunology
Neuropharmacology
Pain - drug therapy
Pain - etiology
Pain Management
Pharmacology. Drug treatments
Prostatic Neoplasms - complications
Prostatic Neoplasms - pathology
Prostatic Neoplasms - therapy
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
Skin - innervation
Tumors
Tumors of the urinary system
Urinary tract. Prostate gland
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Summary:Prostate cancer is unique in that bone is often the only clinically detectable site of metastasis. Prostate tumors that have metastasized to bone frequently induce bone pain which can be difficult to fully control as it seems to be driven simultaneously by inflammatory, neuropathic, and tumorigenic mechanisms. As nerve growth factor (NGF) has been shown to modulate inflammatory and some neuropathic pain states in animal models, an NGF-sequestering antibody was administered in a prostate model of bone cancer where significant bone formation and bone destruction occur simultaneously in the mouse femur. Administration of a blocking antibody to NGF produced a significant reduction in both early and late stage bone cancer pain-related behaviors that was greater than or equivalent to that achieved with acute administration of 10 or 30 mg/kg of morphine sulfate. In contrast, this therapy did not influence tumor-induced bone remodeling, osteoblast proliferation, osteoclastogenesis, tumor growth, or markers of sensory or sympathetic innervation in the skin or bone. One rather unique aspect of the sensory innervation of bone, that may partially explain the analgesic efficacy of anti-NGF therapy in relieving prostate cancer-induced bone pain, is that nearly all nerve fibers that innervate the bone express trkA and p75, and these are the receptors through which NGF sensitizes and/or activates nociceptors. The present results suggest that anti-NGF therapy may be effective in reducing pain and enhancing the quality of life in patients with prostate tumor-induced bone cancer pain.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.can-05-0826