Histological observations on the microenvironment of osteolytic bone metastasis by breast carcinoma cell line.
Bone tissue, with its dynamic microenvironment featuring osteoclastic bone resorption, angiogenesis and matrix degradation, appears to facilitate proliferation of tumor cells after the onset of bone metastasis. In this study, we examined metastatic lesions in the femora of BALB/c nu/nu mice two weeks after intracardiac injection with human breast carcinoma MDA-231 cells. Histopathological observations showed the metastatic lesions close to the chondro-osseous junction, and revealed MDA-231 cells loosely intermingled with different cell types such as osteoblasts, fibroblastic stromal cells, osteoclasts and endothelial cells. In the metastatic nest, many tartrate resistant acid phosphatase (TRAPase)-positive osteoclasts accumulated in direct contact with or were close to alkaline phosphatase (ALPase)- or receptor activator of NF-kappaB ligand (RANKL)-positive osteoblastic cells. It seems likely that osteoclastogenesis is mediated through cell-to-cell contacts with ALPase- and RANKL-expressing osteoblastic cells. Formation of many capillaries lacking complete basal membranes and pericytes ratified the results of in situ hybridization, which revealed intense expression of VEGF in tumor nests, and therefore, indicated ongoing tumor-induced angiogenesis. The tumor cells possessed matrix metallo-proteinases (MMPs)-1 and -9, and frequently extended their stout cytoplasmic processes into fragmented fibrillar components of the growth plate cartilage, implicating degradation of cartilaginous matrix. Thus, osteolytic bone metastasis has demonstrated pathological features as tumor-induced angiogenesis and degradation of extracellular matrix, in addition to osteoclastogenesis. This complex interplay between tumor cells and host tissues may enable and nourish the establishment of a microenvironment that facilitates tumor progression.
Shimamura
Takuya
T
Division of Reconstructive Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
Amizuka
Norio
N
Li
Minqi
M
Freitas
Paulo H L
PH
White
John H
JH
Henderson
Janet E
JE
Shingaki
Susumu
S
Nakajima
Tamio
T
Ozawa
Hidehiro
H
D000818:Animals; D001862:Bone Resorption / Q000473:pathology / Q000503:physiopathology*; D001943:Breast Neoplasms / Q000473:pathology / Q000503:physiopathology*; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000378:metabolism / Q000648:ultrastructure; D005266:Femoral Neoplasms / Q000503:physiopathology* / Q000556:secondary / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D010006:Osteoblasts / Q000378:metabolism* / Q000648:ultrastructure; D010010:Osteoclasts / Q000378:metabolism / Q000648:ultrastructure; D017154:Stromal Cells / Q000378:metabolism