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Results for “Receptors, Autocrine Motility Factor”

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At least 19 recordsLinked to original sources

PubMed1998

The relation between the growth patterns of gastric carcinoma and the expression of hepatocyte growth factor receptor (c-met), autocrine motility factor receptor, and urokinase-type plasminogen activator receptor.

BACKGROUND: Hepatocyte growth factor receptor (c-met), autocrine motility factor receptor (AMFR), and urokinase-type plasminogen activator receptor (uPAR) are known to play important roles in tumor cell migration, invasion, and metastasis. The authors studied the relation between the expression patterns of these genes and the growth patterns of human gastric carcinoma. METHODS: The relation between the expression of c-met, AMFR, and uPAR and clinicopathologic parameters was studied using immunohistochemical preparations from 102 paraffin embedded primary gastric carcinomas. RESULTS: Of 102 cases, 43 (42%) had overexpression of c-met, and AMFR and uPAR immunoreactivity was observed in 41 cases (40%) and 38 cases (37%), respectively. Macroscopic examination revealed that all three genes were expressed in 1 (3%) of 32 early stage gastric carcinomas, 0 (0%) of 29 localized carcinomas (Borrmann types 1 and 2), and 16 (39%) of 41 infiltrating carcinomas (Borrmann types 3 and 4). In particular, the incidence (68%, 13 of 19 cases) of simultaneous expression of the three genes was significantly higher in Borrmann type 4 gastric carcinoma than in the other macroscopic types (P < 0.01). The overexpression of these genes was also closely associated with lymph node metastasis and peritoneal dissemination. In addition, the simultaneous overexpression of the three genes was associated with positive lymphatic vessel invasion and infiltrating type. Patients with tumors that simultaneously expressed all three genes had significantly poorer prognoses than those with tumors expressing only one or two of the genes. Furthermore, the number of genes expressed was closely related to the prognosis, and the Cox proportional hazards model identified this as one of the independent prognostic factors. CONCLUSIONS: These results suggest that the expression patterns of c-met, AMFR, and uPAR may be closely associated with the progression and invasion of gastric carcinoma as well as the prognoses of the patients. Borrmann type 4 gastric carcinoma is characterized by the diverse and simultaneous expression of these three genes.

Adult↗

PubMed1996

Expression of autocrine motility factor receptor in cutaneous malignant melanoma.

BACKGROUND: The autocrine motility factor receptor (AMFR), a specific receptor for AME, is considered to be related to the metastatic potential of tumor cells. OBJECTIVE: We investigated whether AMFR is expressed on cutaneous malignant melanoma cells and has any relationship to clinical stage and metastatic ability. METHODS: We performed an immunohistochemical study on 20 cases of cutaneous malignant melanoma using anti-AMFR antibody. AMFR was expressed in 9 cases (45%), and its expression had a tendency to correlate with the clinical stage and the presence of lymph node metastasis. CONCLUSIONS: The expression of AMFR may have a possible association with the metastatic potential of malignant melanoma.

Biopsy, Needle↗

PubMed2001

Significance of autocrine motility factor receptor gene expression as a prognostic factor in non-small-cell lung cancer.

Autocrine motility factor receptor (AMF-R) has been shown to play an important role in tumor cell migration, invasion and metastasis. We have detected AMF-R expression in tissue specimens from patients with non-small-cell lung cancer (NSCLC) and have assessed their clinical characteristics. Using RT-PCR and immunohistochemistry, we quantified the expression of AMF-R in 47 patients with NSCLC who underwent curative tumor resection, to investigate the relationship between AMF-R expression and clinicopathologic factors and prognosis. RT-PCR results agreed well with the immunohistochemic results (p < 0.0001). In 47 NSCLC patients, 34 (72.3%) samples were evaluated as having high AMF-R gene expression. AMF-R gene expression was significantly associated with lymph node metastasis and stage (p = 0.0295 for lymph node metastasis, p = 0.0152 for stage). The overall survival rate for patients with high AMF-R gene-expressing tumors was significantly worse than for those whose tumors had low AMF-R expression (p = 0.0029). Multivariate analysis also showed that AMF-R gene expression was significantly related to survival (p = 0.0165). These data indicate that AMF-R may contribute to tumor progression and that AMF-R gene expression can serve as a useful prognostic marker in NSCLC.

Adenocarcinoma↗

PubMed1995

Expression of autocrine motility factor receptor in human esophageal squamous cell carcinoma.

Autocrine motility factor and its receptor (gp78) have been shown to play an important role in tumor cell migration, invasion and metastasis. We have detected gp78 expression in buffered-formalin-fixed, paraffin-embedded sections of esophageal squamous cell carcinomas using an anti-gp78 monoclonal antibody (MAb), 3F3A, and examined the relationship between gp78 expression and clinicopathological and prognostic factors. In 55 of 101 (54%) patients, gp78 was detected in the tumor cells. The frequency of gp78-positive expression was significantly associated with tumor size, infiltrative growth, depth of invasion and lymph node metastasis. The cumulative survival rate of patients with gp78 was significantly lower than that of patients without gp78. Our results suggest that autocrine motility factor receptor (gp78) expression could be a useful biomarker for malignancy grading and prognosis in patients with esophageal squamous cell carcinoma.

Adult↗

PubMed2003

Overexpression of autocrine motility factor receptor (AMFR) in NIH3T3 fibroblasts induces cell transformation.

Autocrine motility factor receptor (AMFR) is a cell surface glycoprotein of 78000 molecular weight (gp78), regulating cell motility signaling in vitro and metastasis in vivo. To test whether AMFR could be a common mediator of transformation and oncogenic itself, we transfected NIH3T3 fibroblast cells with expression vectors carrying the full-length cDNA for mouse AMFR and evaluated the effects of increased AMFR on transforming potential. The cells stably expressing high levels of AMFR as a result of transfection displayed a complete morphological change and acquired the ability to grow even in low serum. Furthermore, they were anchorage-independent for growth in soft agar and more motile in phagokinetic track assay. Interestingly, the enhanced expression of AMFR produced tumors in nude mice. Our findings provide a direct evidence that overexpression of the AMFR is associated with the acquisition of a transformation phenotype.

3T3 Cells↗

PubMed2000

Clathrin-mediated endocytosis and recycling of autocrine motility factor receptor to fibronectin fibrils is a limiting factor for NIH-3T3 cell motility.

Autocrine motility factor receptor (AMF-R) is internalized via a clathrin-independent pathway to smooth endoplasmic reticulum tubules. This endocytic pathway is shown here to be inhibited by methyl-(beta)-cyclodextrin (m(beta)CD) implicating caveolae or caveolae-like structures in AMF internalization to smooth ER. AMF-R is also internalized via a clathrin-dependent pathway to a transferrin receptor-negative, LAMP-1/lgpA-negative endocytic compartment identified by electron microscopy as a multivesicular body (MVB). Endocytosed AMF recycles to cell surface fibrillar structures which colocalize with fibronectin; AMF-R recycling is inhibited at 20 degrees C, which blocks endocytosis past the early endosome, but not by m(beta)CD demonstrating that AMF-R recycling to fibronectin fibrils is mediated by clathrin-dependent endocytosis to MVBs. Microtubule disruption with nocodazole did not affect delivery of bAMF to cell surface fibrils indicating that recycling bAMF traverses the MVB but not a later endocytic compartment. Plating NIH-3T3 cells on an AMF coated substrate did not specifically affect cell adhesion but prevented bAMF delivery to cell surface fibronectin fibrils and reduced cell motility. AMF-R internalization and recycling via the clathrin-mediated pathway are therefore rate-limiting for cell motility. This recycling pathway to the site of deposition of fibronectin may be implicated in the de novo formation of cellular attachments or the remodeling of the extracellular matrix during cell movement.

3T3 Cells↗

PubMed1994

Inverse relation of E-cadherin and autocrine motility factor receptor expression as a prognostic factor in patients with bladder carcinomas.

Down-regulation of E-cadherin, an intercellular adhesion molecule, and up-regulation of autocrine motility factor receptor (gp78) expressions have been shown to play a role in tumor cell invasion and metastasis. Monoclonal antibodies against E-cadherin and gp78 were used to stain serial snap-frozen sections of 12 normal bladder and 83 bladder carcinoma specimens (27 noninvasive, 53 invasive, and 3 metastases). In normal urothelium, E-cadherin is expressed while gp78 is not. Positive expression of E-cadherin and negative expression of gp78 were found to be associated with a low risk of clinical progression in the superficial bladder carcinoma patient group. While reduction in E-cadherin concomitantly with an increase in gp78 expression was associated with poor prognosis, 71% of the patients (n = 30) underwent rapid cancer progression, and 32% of the patients died of cancer-related disease at a median of 2 years after initial diagnosis. Thus, it is suggested that reduction of E-cadherin expression associated with an increase in the level of gp78 in bladder cancers may define a high risk group of patients. The dual use of these two antigens may improve early diagnosis of high risk bladder cancer patients and influence treatment decisions.

Aged↗

PubMedDate not supplied

Autocrine motility factor receptor gene expression and cell motility in lung cancer cell lines.

The cell motility of tumor cells is an integral component of tumor invasion and metastasis. Autocrine motility factor (AMF) stimulates cell motility via a receptor (R)-mediated signal pathway. We studied the correlation between level of AMF-R gene expression by reverse transcription-polymerase chain reaction and cell motility by phagokinetic track assay with or without AMF in lung cancer cell lines. Lung cancer cell lines with higher AMF-R gene expression tended to have greater cell motility than those with lower AMF-R gene expression with or without AMF. Most of lung cancer cell lines showed significantly increased motility with the stimulation of AMF. We conclude that the presence of higher AMF-R gene expression and tumor cell motility via receptor in response to the stimulation of AMF could be an important aspect in the invasion and metastasis of lung cancer cell lines.

Carcinoma, Non-Small-Cell Lung↗

PubMed1999

The autocrine motility factor receptor gene encodes a novel type of seven transmembrane protein.

Autocrine motility factor receptor (AMFR) is a cell surface glycoprotein of molecular weight 78,000 (gp78), mediating cell motility signaling in vitro and metastasis in vivo. Here, we cloned the full-length cDNAs for both human and mouse AMFR genes. Both genes encode a protein of 643 amino acids containing a seven transmembrane domain, a RING-H2 motif and a leucine zipper motif and showed a 94.7% amino acid sequence identity to each other. Analysis of the amino acid sequence of AMFR with protein databases revealed no significant homology with all known seven transmembrane proteins, but a significant structural similarity to a hypothetical protein of Caenorhabditis elegans, F26E4.11. Thus, AMFR is a highly conserved gene which encodes a novel type of seven transmembrane protein.

Amino Acid Sequence↗

PubMed2000

Autocrine motility factor receptor expression associates with tumor progression in thymoma.

We assessed the autocrine motility factor receptor (AMFR/gp78) expression in thymoma. AMFR/gp78 antigen was identified in tumor cells in 16 out of 51 (31.4%) thymomas. The AMFR/gp78 expression was closely associated with the stage (I/II vs. III/IV, p<0.0001), pathological subtypes (epithelial vs. other types, p=0.0214), and enhanced expression of alpha-smooth-muscle actin within stroma (p<0. 0001). The outcome of the patients with AMFR/gp78 expression was significantly worse than for those without it (p<0.01). All initial tumors with recurrence expressed AMFR/gp78. The AMFR/gp78 appears to be involved in tumor progression in thymoma.

Actins↗

PubMed2000

Correlation between loss of E-cadherin expression and overexpression of autocrine motility factor receptor in association with progression of human gastric cancers.

Loss of intercellular adhesion and increased cell motility synergistically facilitate tumor cell invasion. We studied these factors in 90 patients with gastric cancers by using an immunohistochemical technique to detect strong or weak expression of E-cadherin (ECD) and autocrine motility factor receptor (AMFR). Normal gastric mucosa (control) reacted strongly for ECD and weakly for AMFR. In study cases, ECD was weak in 47 cases, and AMFR was strong in 39 cases. Weak ECD and strong AMFR expression were associated with tumor dedifferentiation. AMFR expression correlated positively with depth of invasion but not with lymph node metastasis. ECD expression correlated negatively with lymph node metastasis but not with depth of invasion. A strong inverse correlation was found between ECD and AMFR expression. Tumors with weak ECD and strong AMFR expression displayed a more aggressive phenotype than tumors with strong ECD and weak AMFR expression. The postoperative survival of patients with tumors with weak ECD and strong AMFR expression was significantly shorter than that of other groups. Since they are involved in the pathway to development of tumors with a more aggressive phenotype, ECD and AMFR should be examined to evaluate the biologic potential of gastric cancers.

Adenocarcinoma↗

PubMed1996

Autocrine motility factor receptor as a possible urine marker for transitional cell carcinoma of the bladder.

PURPOSE: To determine whether autocrine motility factor receptor (AMFR) is detectable in the urine of patients with transitional cell carcinoma (TCC) of the bladder. MATERIALS AND METHODS: We assayed the urine of 89 patients with bladder pathology and 28 normal controls for AMFR. A monoclonal antibody to AMFR was used. RESULTS: All patients with muscle-invasive TCC tested positive for AMFR. Autocrine motility factor receptor was detectable for 80% of superficial tumors, with a correlation between AMFR and tumor grade. Seventy-five percent of control urines tested negative. CONCLUSIONS: Autocrine motility factor receptor is detectable in the urine of patients with TCC. Long-term follow-up and refinements in the assay should define the marker's utility for detection and prognosis.

Adult↗

PubMed1996

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

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 stage II and III. The results suggest that gp78 expression could be used as a prognostic marker in gastric cancer patients.

Adenocarcinoma↗

PubMed2005

Autocrine motility factor receptor expression implies an unfavourable prognosis in resected stage I pulmonary adenocarcinomas.

BACKGROUND: Pulmonary adenocarcinomas constitute a different histological subtype among the histological subtypes of non small cell lung carcinomas by showing comparably unfavourable rates of prognosis and different immunobiological features. Autonomous motility of tumour cells plays an important role in the regulation of local invasion and distant metastasis of tumour lesions which have great impact on overall survival. AMF (Autocrine motility factor) is a tumour secreted cytokine that stimulates motility during invasion and metastasis via its receptor, AMFR. We conducted an immunohistochemical study to investigate AMFR expression in pulmonary adenocarcinomas and its effect on survival. MATERIAL AND METHODS: We assessed AMFR expression using a monoclonal antibody (3F3A) in a total of 32 surgical specimens with stage I pulmonary adenocarcinomas that underwent curative resection. We analyzed AMFR expression as a possible prognostic factor on survival and its correlations with clinicopathological features. RESULTS: A total of 19 (59.3%) specimens showed AMFR expression. The 3-year survival rates of AMFR positive and AMFR negative patients were 47.3% and 84.6%, respectively, which was a significant difference (P = 0.0197). The univariate predictors of surgical outcome were AMFR expression (P = 0.032) and perineural invasion (P = 0.038). However, multivariate analysis revealed AMFR expression (P = 0.045) as the only independent prognostic factor. CONCLUSIONS: AMFR expression predicts an unfavourable surgical outcome in patients with stage I pulmonary adenocarcinomas.

Adenocarcinoma↗

PubMed1994

Expression of autocrine motility factor receptor in colorectal cancer as a predictor for disease recurrence.

BACKGROUND: New biologic prognostic factors are needed to guide the treatment of patients with colorectal cancer. The prognostic value of the altered expression of the cell surface glycoprotein gp78, which has been implicated in tumor-cell invasion and metastasis as an autocrine motility factor (AMF) receptor, was evaluated. METHODS: The level of expression of AMF receptor gp78 was analyzed immunohistochemically in tumor specimens from 118 patients who had undergone surgery for colorectal cancer. Multivariate analysis was used to determine whether gp78 expression status was correlated with patient prognosis. RESULTS: Among the 118 patients studied, the 5-year survival rate for the 51 patients who had gp78-positive tumors was significantly poorer that that of the 67 patients who had gp78-negative tumors (49.8% vs. 89%). The incidence of gp78 positivity was correlated with tumor progression as reflected by histologic type, depth of invasion, lymph node metastasis, vessel invasion, and tumor stage. Among the 101 patients who underwent curative resection, the difference in disease free survival between patients with gp78-positive tumors and those with gp78-negative tumors was significant. This significant difference remained among patients who had Stage II tumors. Multivariate analysis with the Cox regression model indicated that gp78 positivity was a good predictor of disease recurrence, ranking with extent of tumor invasion (T classification) and lymph node status (N classification). CONCLUSIONS: Increased expression of gp78 is correlated with a high incidence of recurrence and, consequently, with decreased survival of patients with colorectal cancer. Expression of gp78 might be of prognostic value in these patients.

Adult↗

PubMed1998

Localization of autocrine motility factor receptor to caveolae and clathrin-independent internalization of its ligand to smooth endoplasmic reticulum.

Autocrine motility factor receptor (AMF-R) is a cell surface receptor that is also localized to a smooth subdomain of the endoplasmic reticulum, the AMF-R tubule. By postembedding immunoelectron microscopy, AMF-R concentrates within smooth plasmalemmal vesicles or caveolae in both NIH-3T3 fibroblasts and HeLa cells. By confocal microscopy, cell surface AMF-R labeled by the addition of anti-AMF-R antibody to viable cells at 4 degreesC exhibits partial colocalization with caveolin, confirming the localization of cell surface AMF-R to caveolae. Labeling of cell surface AMF-R by either anti-AMF-R antibody or biotinylated AMF (bAMF) exhibits extensive colocalization and after a pulse of 1-2 h at 37 degreesC, bAMF accumulates in densely labeled perinuclear structures as well as fainter tubular structures that colocalize with AMF-R tubules. After a subsequent 2- to 4-h chase, bAMF is localized predominantly to AMF-R tubules. Cytoplasmic acidification, blocking clathrin-mediated endocytosis, results in the essentially exclusive distribution of internalized bAMF to AMF-R tubules. By confocal microscopy, the tubular structures labeled by internalized bAMF show complete colocalization with AMF-R tubules. bAMF internalized in the presence of a 10-fold excess of unlabeled AMF labels perinuclear punctate structures, which are therefore the product of fluid phase endocytosis, but does not label AMF-R tubules, demonstrating that bAMF targeting to AMF-R tubules occurs via a receptor-mediated pathway. By electron microscopy, bAMF internalized for 10 min is located to cell surface caveolae and after 30 min is present within smooth and rough endoplasmic reticulum tubules. AMF-R is therefore internalized via a receptor-mediated clathrin-independent pathway to smooth ER. The steady state localization of AMF-R to caveolae implicates these cell surface invaginations in AMF-R endocytosis.

3T3 Cells↗

PubMed1996

Expression and function of autocrine motility factor receptor in human choriocarcinoma.

OBJECTIVE: Our purpose was to determine whether human choriocarcinoma cells express autocrine motility factor receptor (AMF-R) and to study its function in this tumor system. STUDY DESIGN: The expression and localization of AMF-R were compared in choriocarcinoma and normal placental trophoblasts using both cell lines and tissue sections. In addition, migratory properties of choriocarcinoma cells and normal placental cells was determined. RESULTS: Using immunofluorescence and immunoperoxidase staining, we have detected the expression of AMF-R in choriocarcinoma cells with receptor clustering on the cell surface, while term placenta cells expressed AMF-R less intensely with no receptor clustering. In choriocarcinoma tissues, AMF-R was strongly expressed in malignant cytotrophoblasts cells while adjacent normal villous trophoblast cells and necrotic regions were weakly or negatively stained. Choriocarcinoma cells responded to AMF-R stimulation with increased cell motility, while term placental cells were unresponsive. CONCLUSION: Human choriocarcinoma cells express functional cell surface AMF-R in vitro and in choriocarcinoma tissue suggesting that this receptor may play an important role in cancer cell motility.

Cell Movement↗

PubMed2001

Autocrine motility factor receptor expression in patients with stage I non-small cell lung cancer.

BACKGROUND: Expression of autocrine motility factor receptor (AMFR) associates with increased cell migration and poor survival in certain types of human cancers. We assessed the possible correlation between AMFR, clinicopathologic features, and survival in stage I non-small cell lung cancer (NSCLC). METHODS: AMFR expression was analyzed immunohistochemically, using a monoclonal antibody (3F3A) in tumor specimens from 97 patients with curative resection. Vascular endothelial growth factor (VEGF) expression was also examined after accounting for AMFR expression. RESULTS: Out of 97 tumors, 38 (39.2%) were positively stained with AMFR. The AMFR expression was significantly associated with histologic type of tumor, mainly in adenocarcinoma. Overall survival of patients with AMFR-positive tumors was significantly worse than that of AMFR-negative tumors (p = 0.0050). The AMFR expression appears to be associated with VEGF expression. Patients who were AMFR positive and had high VEGF expression had a worse prognosis compared with the AMFR-negative and low VEGF-expression group (p < 0.0001). Multivariate analysis revealed an independent prognostic impact of AMFR on survival (p = 0.0039). CONCLUSIONS: These results indicate that evaluation of AMFR expression may provide useful guidance in follow-up of patients with NSCLC.

Aged↗