Bone resorption activity of osteolytic metastatic lung and breast cancers

Abstract

Production of bone resorption mediators and bone resorption activity were compared among osteolytic metastatic cancers, normal bone tissues, and soft tissue metastatic cancers to search for the possible factors leading to cancer-induced bone resorption. Twenty-five patients with untreated osteolytic metastatic breast or non-small cell lung cancers consisted of the study group. Normal bone tissues obtained from the same patient were used as internal controls; and tumor tissues from patients with soft tissue metastasis were used as external controls. Serum and urinary bone turnover markers were measured. Tissues harvested during surgery were subjected to tissue culture. The levels of prostaglandin E2 ( PGE2), tumor necrosis factor-a (TNF-a), and interleukin-6 (IL-6) in the supernatant after 72 h of culture were measured. Bone resorption activity was measured by calcium release from cultured calvarias, and bone volume as well as osteoclast number in bone sections. Patients with osteolytic metastatic cancers showed significantly decreased serum osteocalcin, increased serum alkaline phosphatase, and urinary deoxypyridinoline levels. Osteolytic metastatic cancers produced significantly more PGE2 than both controls. Conditioned medium from osteolytic metastatic tumors showed significantly enhanced bone resorption activity, and indomethacin significantly reduced this activity. Levels of PGE?, and bone resorption activity increased in osteolytic tumor tissues than soft tissue metastatic tissues in the same patient indicated that the same tumor cells might respond differently to different microenvironments. Our observation showed that PGE2 was produced by osteolytic metastatic cancers and stimulated bone resorption in mice calvarias. PGEz inhibitor may be applicable in reducing bone resorption by osteolytic metastatic cancers.

Early urine proteome changes in an implanted bone cancer rat model

“…It is the most widely used transplantable tumor in experimental research. The cells can cause significant bone resorption and bone destruction at the site of rat bone implantation this is consistent with the phenotype of bone metastasis in breast cancer patients (Shih et al, 2004). In this experiment, we implanted Walker 256 cells into the left tibia of the rat.…”

Reawakening of dormant estrogen-dependent human breast cancer cells by bone marrow stroma secretory senescence

“…IL-6 may also induce relative chemotherapy resistance through Akt, myeloid leukemia cell differentiation protein-1 (Mcl-1) and TNF-related apoptosis-inducing ligand (TRAIL) [ 70 – 72 ] and modulation of B-cell lymphoma-2-associated X protein Long (BclXL) and (bcl-2-like protein 4) (BAX), [ 73 ]. IL-6 and IL-8 also enable the microenvironment to promote cancer progression by promoting migration and matrix metalloprotease (MMP) production in dermal fibroblasts [ 74 ], bone resorption and osteolytic metastases though cyclooxygenase-2 (Cox-2)/prostaglandin E2 (PGE2) [ 75 , 76 ]. It is evident that these cytokines, as well as growth factors, activate different signal pathways, often depending on whether an epithelial or mesenchymal program is activated in a particular cell.…”

Values of alkaline phosphathase and their isoenzyme profiles in patients with cancer in respect to bone and liver metastasis

“…Approximately 70% of patients with advanced cancer will develop bone metastases (13)(14)(15)(16)(17). Approximately 70% of patients with advanced cancer will develop bone metastases (13)(14)(15)(16)(17).…”