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

Abstract

The preferential proliferation of cancer cells in the bone microenvironment is poorly characterised. Expression pattern of bone marrow and other organ microenvironment in contact with osteolytic (Walker W256) and osteoblastic (MatLyLu MLL) metastases were investigated. Fisher and Copenhagen rats received, respectively, W256 and MLL cells injection. Bone and soft tissues were analysed by immunochemistry for DKK1, cathepsin K, RANKL, MCSF or IL6 expression. Tartrate-resistant acid phosphatase (TRAcP)-positive cells were detected by a histoenzymatic technique. In bone, expressions of MCSF and DKK1 were shown in stromal cells of the bone marrow, in contact with metastatic foci of both tumours. Many stromal cells were found RANKL positive in the vicinity of the tumours. Cells expressing cathepsin K and multinucleated TRAcP þ cells were found in direct contact with trabeculae but also in bone marrow spaces near metastatic cells. In extraosseous tumours, cells in contact with malignant cells did not expressed DKK1, MCSF, cathepsin K and IL6. Some RANKL þ cells were found in the periphery of subcutaneous tumours but may represent Langerhans cells. Abnormal presence of TRAcP þ cells was never observed in the vicinity of malignant cells. Interaction between stromal and cancer cells induces the expression on the formers of characteristics leading to osteoclastogenesis only in the bone microenvironment.

Glucose-dependent insulinotropic polypeptide receptor deficiency leads to modifications of trabecular bone volume and quality in mice

“…Animals were injected intraperitoneally with calcein (10 mg/kg) seven and two days before necropsy. Blood samples were collected from the cut tip of the tail vein (~200 μl) of conscious mice prior to sacrifice by lethal inhalation with CO 2 and tibias were then harvested and processed as previously described [18].…”

Pharmacologic inhibitors of IκB kinase suppress growth and migration of mammary carcinosarcoma cellsin vitroand prevent osteolytic bone metastasisin vivo

“…In view of this, pharmacologic inhibitors of IKKα and IKKβ might be expected to be of particular value in the prevention of osteolytic disease, but the effects of IKK inhibitors on bone metastases have not been previously investigated. Here, we investigated the effects of these inhibitors in a well-established model of metastatic bone disease associated with breast cancer induced by intracardiac injection of W256 mammary carcinosarcoma cells (20,21).…”

Breast Cancer Metastases to Bone: Role of the Microenvironment

“…One of the mediators of these changes was shown to be the tumour-overexpressed CCN3, that can inhibit osteoblast differentiation and shift the RANKL/OPG ratio to favour osteolysis (147). Another osteoblast-produced osteoclastogenic factor, MCSF, has also been implicated in breast cancer metastases to bone (148).…”