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

Abstract

Osteonectin 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 10(5) cells were injected i.v., median colony value was 55 and 20 in higher expressor vs. lower expressor respectively (p less than 0.005). Spontaneous metastasis indicates a possible reverse correlation. Our data align osteonectin with other matrix-components and adhesion molecules in affecting potential metastatic spreading of transformed cells.