Prostate carcinoma skeletal metastases: cross-talk between tumor and bone.
The majority of men with progressive prostate cancer develop metastases with the skeleton being the most prevalent metastatic site. Unlike many other tumors that metastasize to bone and form osteolytic lesions, prostate carcinomas form osteoblastic lesions. However, histological evaluation of these lesions reveals the presence of underlying osteoclastic activity. These lesions are painful, resulting in diminished quality of life of the patient. There is emerging evidence that prostate carcinomas establish and thrive in the skeleton due to cross-talk between the bone microenvironment and tumor cells. Bone provides chemotactic factors, adhesion factors, and growth factors that allow the prostate carcinoma cells to target and proliferate in the skeleton. The prostate carcinoma cells reciprocate through production of osteoblastic and osteolytic factors that modulate bone remodeling. The prostate carcinoma-induced osteolysis promotes release of the many growth factors within the bone extracellular matrix thus further enhancing the progression of the metastases. This review focuses on the interaction between the bone and the prostate carcinoma cells that allow for development and progression of prostate carcinoma skeletal metastases.
Keller
E T
ET
Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, USA. etkeller@umich.edu
Zhang
J
J
Cooper
C R
CR
Smith
P C
PC
McCauley
L K
LK
Pienta
K J
KJ
Taichman
R S
RS
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D001859:Bone Neoplasms / Q000378:metabolism / Q000556:secondary*; D002118:Calcium / Q000378:metabolism; D019743:Chemokines, CXC / Q000378:metabolism; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D044162:Parathyroid Hormone-Related Protein; D036361:Peptide Hormones / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism
D019485:Bone Morphogenetic Proteins; D019743:Chemokines, CXC; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D036361:Peptide Hormones; D020782:Matrix Metalloproteinases; D002118:Calcium