Soluble ErbB3 levels in bone marrow and plasma of men with prostate cancer.
OBJECTIVE
Prostate cancer tends to metastasize to bone and induce osteoblastic lesions. We identified a soluble form of ErbB3 (sErbB3), p45-sErbB3, in bone marrow supernatant from men with prostate cancer bone metastasis and showed that p45-sErbB3 enhances bone formation. We aimed to understand clinical implications of sErbB3 by establishing an ELISA to detect sErbB3 levels in bone marrow and plasma samples.


METHODS
We did ELISAs on marrow from 108 men [34 with androgen-dependent disease, 30 with androgen-independent disease (AI) but negative bone scan (AI/BS-), and 44 with AI and positive bone scan (AI/BS+)], sequential marrow from 5 men during treatment, plasma from 52 men before and after docetaxel treatment, and plasma from 95 men ages > or =70 years old without prostate cancer.


RESULTS
Some men with clinically detectable bone metastasis had high sErbB3 levels. Within the AI/BS- group, higher sErbB3 levels seemed to yield lower rates of bone metastasis. In the AI/BS+ group, detectable bone metastases took longer to appear in men with higher sErbB3 levels than in men with lower sErbB3 levels (median, 82 versus 41 months). However, high sErbB3 levels did not confer survival benefit after metastasis development. Among men with metastatic progression in bone, docetaxel treatment reduced plasma sErbB3 (P < 0.0001) but did not affect bone-specific alkaline phosphatase (P = 0.206) or prostate-specific antigen (P = 0.906). sErbB3 was also detected in men without prostate cancer.


CONCLUSIONS
The apparent correlation between higher sErbB3 levels and longer time to bone metastasis suggests that sErbB3 participates in progression in bone of prostate cancer.
Lin
Sue-Hwa
SH
Department of Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. slin@mdanderson.org
Lee
Yu-Chen
YC
Choueiri
Michel B
MB
Wen
Sijin
S
Mathew
Paul
P
Ye
Xiangcang
X
Do
Kim-Anh
KA
Navone
Nora M
NM
Kim
Jeri
J
Tu
Shi-Ming
SM
Yu-Lee
Li-Yuan
LY
Logothetis
Christopher J
CJ
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001859:Bone Neoplasms / Q000556:secondary; D018450:Disease Progression; D000077143:Docetaxel; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000097:blood* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D020893:Receptor, ErbB-3 / Q000032:analysis / Q000097:blood* / Q000378:metabolism*; D012995:Solubility; D016019:Survival Analysis; D043823:Taxoids / Q000494:pharmacology
D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D020893:Receptor, ErbB-3