A secreted phosphoprotein marker for neoplastic transformation of both epithelial and fibroblastic cells

Abstract

A wide variety of virally and spontaneously transformed fibroblasts secrete a major transformation-related phosphoprotein with a molecular weight (MW), depending on the species of origin, of about 62,000 (62K). Markedly elevated extracellular levels of this major 32P-labelled protein are not simply linked to exponential growth but instead are associated directly with transformation. The phosphoprotein is not antigenically related to p60src, p60c-src or simian virus 40 (SV40) non-viral T antigen, and it is further distinguishable from SV40 non-viral T antigen (pp 53) on the basis of its electrophoretic mobility. In this study we have compared a variety of normal and transformed epithelial cells for secretion of this 32P-labelled protein and have found that this marker distinguishes neoplastic from preneoplastic and normal mouse mammary epithelium and also identifies highly tumorigenic cells derived from guinea pig bile duct epithelium and rat liver epithelium. Because the classical phenotypic properties commonly associated with transformation of fibroblasts cannot be generally used to discriminate tumorigenic from non-tumorigenic epithelial cells, this phosphoprotein, which identifies tumorigenic cells of both fibroblastic and epithelial origin, is likely to be of particular importance.

The Integrin α9β1 Binds to a Novel Recognition Sequence (SVVYGLR) in the Thrombin-cleaved Amino-terminal Fragment of Osteopontin

“…The biological significance of the thrombin-cleaved fragment that is present in vivo has not been previously determined (16,17). The results of this study together with the previous report provide insights into the potential physiological role of thrombin cleavage.…”

“…Upon thrombin cleavage of osteopontin at sites of inflammation or remodeling, the generation of an ␣ 9 ␤ 1 ligand could thus enhance the cell migration and proliferation that are required for tissue remodeling to occur. In addition, osteopontin has another thrombin cleavage site at Arg 160 -Gly 161 (16). The sequence of the fragment produced by cleavage at both sites would be GDSVVYGLR, a fragment that would be expected to inhibit ␣ 9 ␤ 1 -mediated effects on cell behavior, and thereby potentially contribute to the termination of the events described above.…”

“…Osteopontin is present at high concentrations in diseases associated with tissue remodeling, including granuloma formation (12) and coronary restenosis (13,14), suggesting that this molecule might contribute to the process of remodeling. Osteopontin contains a predicted thrombin cleavage site (15) and appears to be cleaved at this site in vivo (16,17). Several integrins have been identified as osteopontin receptors.…”

The Role of Osteopontin in Tumor Progression and Metastasis in Breast Cancer

“…Osteopontin is usually absent or expressed at a low level in normal tissues but is up-regulated in certain preneoplastic and neoplastic epithelia (28,123,124), including that of the breast (125). Transfection of an expression vector for osteopontin induces malignant transformation and induction of metastasis in a benign rat mammary epithelial cell line (126), whereas transfection of osteopontin antisense cDNA inhibits these processes in a cell line already overexpressing osteopontin (127,128).…”

Osteopontin induces increased invasiveness and plasminogen activator expression of human mammary epithelial cells

“…Studies have shown that OPN may be synthesized by tumor-in®ltrating macrophages (Brown et al, 1994;Hirota et al, 1995) and by breast cancer cells themselves (Senger et al, 1983;Morris et al, 1993;Bautista et al, 1994;Tuck et al, 1998), although the relative biologic signi®cance of these di erent potential sources of OPN is not yet understood. Previous work (Xuan et al, , 1995Senger and Perruzzi, 1996) has shown that some breast cancer cells show integrin-dependent adhesion to, and migratory response to OPN.…”