Histological observations on the microenvironment of osteolytic bone metastasis by breast carcinoma cell line

Abstract

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-κB 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.Bone metastasis is an important clinical entity in patients suffering from some sorts of malignant tumors, and blood circulation comes out as a vector for tumor cells to spread and establish metastatic lesions. Noteworthy is the venous drainage from the breast directly into the vertebral venous plexus, which may explain the high rates of bone metastasis by breast carcinoma cells. Bone microenvironment per se also seems to play an important role, facilitating colonization and proliferation of tumor cells. Breast carcinomas show a trend toward bone metastasis, especially if compared to fewer bone metasta-

Distribution of macrophages, osteoclasts and the B-lymphocyte lineage in osteolytic metastasis of mouse mammary carcinoma

“…Breast car-easily observe macrophage/monocytes, lymphocytes and osteoclasts which localize at metastatic sites. F4/80 can recognize macrophage/monocyte lineage cells, but not osteoclasts in mouse bone as reported previously (34,43). In contrast, tartrate-resistant acid phosphatase (TRAP) staining can distinguish the osteoclastic lineage from mouse macrophage/ monocytes, though not from human macrophages which can express TRAP5a.…”

Interactions between microenvironment and cancer cells in two animal models of bone metastasis

“…Carcinoma-associated fibroblasts are implicated in extracellular matrix production, which provides a lattice that facilitates cancer progression; they are one of the main sources of VEGF, thus providing more nutriment to the metastastic cells (Kalluri and Zeisberg, 2006). Shimamura et al (2005) have investigated the microenvironment of osteolytic metastases caused by MDA-MB 231 breast carcinoma cells in nude mice. At 2 weeks after an intracardiac injection with MDA-MB 231 cells, foci of tumour cells were associated with osteoclastogenesis together with angiogenesis related to intense the expression of VEGF (Shimamura et al, 2005).…”

“…Shimamura et al (2005) have investigated the microenvironment of osteolytic metastases caused by MDA-MB 231 breast carcinoma cells in nude mice. At 2 weeks after an intracardiac injection with MDA-MB 231 cells, foci of tumour cells were associated with osteoclastogenesis together with angiogenesis related to intense the expression of VEGF (Shimamura et al, 2005). In our study, we have also found specific modifications in the bone microenvironment around the tumour foci with expression of M-CSF, Dkk-1 and RANKL in non-osteoblastic cells.…”

Magnetite Nanoparticles for Cell Lysis Implanted Into Bone - Histological and TEM Study

“…They rapidly become resistant to chemotherapy and radiotherapy and are often very painful necessitating local and/or alternative treatments in order to reduce the osteolysis triggered by the cancerous cells. The osteolysis is due to local activation of the osteoclasts and macrophages by factors synthesized by the tumor cells (Shimamura, T., et al, 2005). It is the osteolysis that is very often responsible for the pain.…”