Expression of autocrine motility factor receptor correlates with disease progression in human gastric cancer

Abstract

Summary Up-regulation of autocrine motility factor receptor (AMF-R) expression has been shown to be associated with invasion and metastasis of experimental tumour systems and human neoplasms. Monoclonal antibodies against AMF-R (gp78) were used to stain 221 primary gastric cancer specimens, and level of expression was examined in relation to pathological stage and prognostic values. In 125 out of 221 (56.6%) patients, gp78 was detected. Expression of gp78 was associated with macroscopic type, lymphatic and venous invasions, and lymph node and peritoneal metastasis. The level of gp78 expression in the cancer specimens was associated with histopathological stage and grade of tumour penetration. Positive gp78 expression was significantly associated with poor prognosis (P<0.001). This significant relationship remained among patients in stages II and III. The results suggest that gp78 expression could be used as a prognostic marker in gastric cancer patients.Keywords: gastric cancer; autocrine motility factor receptor; cell motility; invasion; metastasis The incidence of gastric carcinoma is the highest of all carcinomas, and it is the leading cause of death from cancer in Japan. In spite of the improvement in surgical treatment and chemotherapy, the prognosis in this disease is still poor owing to local recurrence or metastasis (Baba et al., 1995; Bonenkamp et al., 1995;Hallissey et al., 1994;Nakazato et al., 1994).Many investigators study the mechanism of tumour cell invasion and metastasis to better understand local recurrence and metastasis (Nekarda et al., 1994;Nomura et al., 1995; Sato et al., 1994; Yonemura et al., 1995). Among the various steps of invasion or metastasis of the cancer cell, cell motility is one of the important factors that promotes cancer progression (Fidler, 1990;Hart et al., 1989;Liotta et al., 1986;Nabi et al., 1991). However, the relationship between gastric cancer stages and cell motility-regulated factors has not been reported. Thus, it is of obvious interest to study such parameters in order to obtain an insight into the biological behaviour of gastric cancers.Autocrine motility factor (AMF) is a cytokine that is produced and secreted by cancer cells and that stimulates both random and directed cell migration through binding to its receptor, a 78 kDa cell surface glycoprotein (gp78, AMF receptor) (Liotta et al., 1986;Nabi et al., 1990Nabi et al., , 1991Silletti et al., 1991). Recently, a molecular cloning of AMF receptor (AMF-R) was reported (Watanabe et al., 1991a). Expression of this receptor relates to cell motility-regulating effects and also may play an important role in tumour cell invasion or metastasis (Nabi et al., 1992;Watanabe et al., 1991b). Recent studies have demonstrated that increased expression of gp78 is correlated with a high incidence of recurrence and decreased survival of patients with colorectal cancer, bladder cancer and oesophageal cancer (Nakamori et al., 1994;Otto et al., 1994;Maruyama et al., 1995).Here, we studied the expression of gp78 in specimens from ...

Glycolysis inhibition for anticancer treatment

“…Autocrine motility factor and its receptor AMFR (gp78) were originally identified in melanoma and oncogenetransfected metastatic NIH3T3 cells, and the AMF/ AMFR interaction seems to stimulate tumor cell migration in vitro and enhance metastasis and angiogenesis in vivo (Liotta et al, 1986;Nabi et al, 1990;Watanabe et al, 1996;Funasaka et al, 2001Funasaka et al, , 2002. Autocrine motility factor receptor is overexpressed in various metastatic tumors and is correlated with a poor prognosis (Hirono et al, 1996). The presence of GPI in serum and urine is associated with cancer progression and indicates poor prognosis (Baumann and Brand, 1988;Baumann et al, 1990;Filella et al, 1991).…”

Immunohistochemical expression of Type IV Collagen and Autocrine Motility Factor Receptor in Odontogenic Tumours

“…In normal physiological status, motility is tightly regulated, whereas tumour cell motility may be aberrantly regulated or auto regulated. Tumour-secreted or autocrine factors, like AMF or autotaxin, may be involved in this autoregulation [4]. Whether Collagen IV and Autocrine Motility Factor Receptor (AMFR) play an important role in the different odontogenic tumours is still unknown.…”

Expression of Autocrine Motility Factor Correlates with the Angiogenic Phenotype of and Poor Prognosis for Human Gastric Cancer

“…The physiologic functions of these regulators have not been fully established, but available data suggest that they may be involved in fetal development and/or tissue repair (3,4). AMF expression is detected in various types of normal fibroblast and epithelium as well as tumor cells (5 -7).…”