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Background: Surgery, chemotherapy and radiotherapy are the mainstay of tumor management. However, in systemic disease cure can be achieved in yet a few tumor entities. Based on cell biological research we have characterized the process of tumor progression and metastasis and disclosed that the loss of cell-cell adhesion in association with an increased tumor cell motility is an essential feature of the malignant potential of a tumor., Methods: According to this principle we derived therapeutical methods differing from hitherto existing treatments by being exclusively focused on tumor cell motility. Characterization of so-called anti-motility factors was performed biochemically as well as with motility assays by in vitro studies in established bladder carcinoma cell lines., Results: We evaluated the potential therapeutic benefit in a model of chemically induced bladder carcinoma followed by a phase I/II trial applying antimotility factors in patients with advanced bladder cancer., Conclusion: Both basic research as well as the results of first clinical trials confirm, that advanced carcinomas can be influenced by inhibition of tumor cell motility., (Copyright 2002 S. Karger GmbH, Freiburg)

Seventeen patients with endometrial cancer were studied. Tissues of primary (P) and metastatic (M) lesions were obtained from 8 patients and complete sets of P, M and Recurrent (R) lesions were obtained from 9 patients during a follow-up period of 1-10 years. Expressions of estrogen receptors, progesterone receptors, multidrug resistance protein-1, multidrug resistance-related protein, c-erbB-2, membrane-type metalloproteinase, human telomerase RNA, human telomerase reverse transcriptase RNA, E-cadherin and autocrine motility factor receptor were studied by RT-PCR. Also, telomeric restriction fragment length (TRFL) and microsatellite instability were determined between P, M and R. The results indicate that there are significant differences in the gene expression frequency during tumor progression. The mismatch rate ranged from 0 to 47.1% between P and M and from 14.3% to 66.7% between P and R, respectively. The TRFL analysis showed a marked reduction in P and M (P vs. M: 8.2 +/- 0.9 vs. 5.6 +/- 0.4 kb, mean +/-SEM, n = 9, p = 0.002 by paired Student's t test). The length further decreased in R (P vs. R: 8.2 +/- 0.9 vs. 3.2 +/- 0.7, p = 0.01, M vs. R: 5.6 +/- 0.4 vs. 3.2 +/- 0.7, p = 0.005). The genomic instability/replication error was tested by AluI arbitrary primed polymerase chain reaction (AP-PCR). Five out of 17 patients showed an altered replication error pattern (29.4%). The mean number of abnormal AluI AP-PCR patterns in M and R compared to the P was 1.5 (M) and 4 (R). The difference between the P and R was statistically significant (p < 0.04). The present data indicate that biological behavior of cancer cells in P, M and R may differ significantly.

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.