Expression of autocrine motility factor receptor in serum‐ and protein‐independent fibrosarcoma cells: Implications for autonomy in tumor‐cell motility and metastasis

Abstract

The motile response of serum-dependent (Gc-4 SD) and protein-independent (Gc-4 PF) murine fibrosarcoma cells to monoclonal antibody (MAb) that binds to gp78 a cell-surface receptor (M(r) 78,000) for an autocrine motility factor (AMF) was analyzed. The Gc-4 PF cells responded to the anti-gp78 by increased motility in vitro (3-fold) and increased lung colonization in vivo (8- to 20-fold), while the serum-dependent counterpart failed to respond to motile stimulation both in vitro and in vivo. Immuno-analysis of cell-surface expression and cell extracts revealed a smaller amount of gp78 in Gc-4 SD cells than in Gc-4 PF cells. Both cell lines secrete an equal amount of AMF to the culture media. Our results suggest that protein-free culture of Gc-4 PF cells is associated with high response to AMF and with high expression of its receptor, and that autonomous motile regulation may play a role in tumor dissemination.

Overexpression of autocrine motility factor in metastatic tumor cells: possible association with augmented expression of KIF3A and GDI-β

“…The expression of gp78 was found in Gc-4 PF cells as described previously, 18 and was augmented by transfection with Adamf/phi in a dose-dependent manner (Figure 4a). In contrast, no expression of gp78 was observed in DPF cells even in the cells transfected by amf/phi gene at 100 MOI (Figure 4b), suggesting absence of the receptor for AMF in DPF cells.…”

“…One was a murine fibrosarcoma cell line, Gunma clone-4 protein-free (Gc-4 PF), 5 in which the motility and metastatic capacity show high responses to AMF by increased expression of the receptor. 18 Another was Dunn osteosarcoma protein free (DPF), a mouse osteosarcoma cell line. 33 Gc-4 PF cells were cultured in RPMI 1640 medium without serum.…”

“…15,16 AMF binds to a unique 78 kDa glycoprotein receptor, and initiates gp78 phosphorylation. 4,17 Anti-gp78 monoclonal antibody (3F3A) stimulates motility of metastatic tumor cell, 18 and reveals the localization of gp78 on the leading lamella as well as the trailing edge of motile cells. 19 The expression of gp78 is a predicting factor for prognosis in patients with various malignant neoplasms including esophageal, colorectal, bladder, gastric, and lung carcinoma.…”

Influence of Antiestrogens on NIH-3T3-Fibroblast-Induced Motility of Breast Cancer Cells

“…The metastatic dissemination of tumor cells to secondary sites requires highly motile cancer cell behavior which appears to be influenced by growth factors, cytokines, and other molecules yet to be identified [2,3]. We and others have demonstrated that 3T3-CM, which is used as a chemoattractant in the Matrigel invasion chamber assay, contains a number of motility factors that increase the invasiveness of breast cancer cells [5,6].…”

“…The motile behavior of tumor cells appears to be regulated, in part, by growth factors and cytokines [2,3]. Stromal tissue surrounding the tumor cells produces growth factors which are known to enhance tumor cell proliferation and progression to a metastatic phenotype [4].…”