Osteonectin transcript and metastatic behavior in v-Ki-ras transformed fibroblasts

Abstract

Osteoqectin is one of the major non-collagenous proteins of bone. However, its transcript has been found in many soft, extracellular matrix-producing tissues; an osteonectin-related protein was detected in tumor basement membrane. We have investigated the expression of osteonectin gene in fresh BALB/c fibroblasts transformed by v-Ki-ras. Transformed cells exhibited lower levels of RNA as compared with normal fibroblasts. The transformed cells were cloned after in vivo tumorigenic assay, and 4 clones were analyzed for osteonectin expression by Northern blots. Two of them were selected for high or low osteonectin expression and tested in vivo in spontaneous and artificial metastasis assays. High osteonectin expression was correlated with high lung colonization. When 10s cells were injected i.v., median colony value was 55 and 20 in higher expressor vs. lower expressor respective (p < 0.005). Spontaneous metastasis indicates a possible reverse correlation. Our data align osteonectin with ot R er matrix-components and adhesion molecules in affecting potential metastatic spreading of transformed cefls.

Endogenous Osteonectin/SPARC/BM-40 Expression Inhibits MDA-MB-231 Breast Cancer Cell Metastasis

“…The promoting or inhibiting effects of osteonectin in different cancers seem dependent upon the cell type, the concentration, and the presence of full-length or proteolytic fragments of osteonectin (9). Although osteonectin promotes melanoma and squamous cell tumor growth (10,11) and glioma invasion (12), there are reports that decreased osteonectin expression is associated with increased tumorigenicity and metastasis of human ovarian carcinoma cells (13) as well as transformed fibroblasts (14,15). In neuroblastomas, expression of osteonectin is inversely correlated with malignant progression, and treatment of these tumors with osteonectin results in impaired tumor growth in vivo (16).…”

Stimulation of Motility of Human Renal Cell Carcinoma by SPARC/Osteonectin/BM-40 Associated with Type IV Collagen

“…SPARC has been detected in malignant tumor tissues [12][13][14][15][16] and cell lines [17]. SPARC antisense expression vector introduction results in a decrease in both in vitro adhesive and invasive capacities, and in vivo tumorigenicity of B16 melanoma cells [18].…”

Pathogenesis of Bone Metastases: Role of Tumor-Related Proteins

“…Osteonectin is a multifunctional glycoprotein produced by osteoblasts and other cell types that plays a role in mineralization, cell‐to‐matrix adhesion, and angiogenesis. Osteonectin is produced by both prostate and breast cancer, in addition to other tumors including malignant melanomas and fibroblasts transformed with v‐Ki‐ ras (37–39) . Osteonectin promotes invasion and metastasis by enhancing matrix metalloproteinase activity in breast and prostate cancers (29)…”

“…Osteonectin is produced by both prostate and breast cancer, in addition to other tumors including malignant melanomas and fibroblasts transformed with v-Ki-ras. (37)(38)(39) Osteonectin promotes invasion and metastasis by enhancing matrix metalloproteinase activity in breast and prostate cancers. (29) BSP BSP is a secreted glycoprotein produced by osteoblasts, is present in bone matrix, and is produced by certain osteotropic cancers, such as breast, prostate, thyroid, and lung cancer.…”