Tumor cell motility as a novel target in cancer--experimental and clinical results.
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.


CONCLUSIONS
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.
Otto
T
T
Klinik für Urologie, Med. Einrichtungen der Universität Essen, Essen, Germany.
Luemmen
G
G
Bex
A
A
Suhr
J
J
Goebell
P J
PJ
Raz
A
A
Ruebben
H
H
D000328:Adult; D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015820:Cadherins / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D011379:Prognosis; D060285:Receptors, Autocrine Motility Factor; D018121:Receptors, Cytokine / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D044767:Ubiquitin-Protein Ligases; D001749:Urinary Bladder Neoplasms / Q000473:pathology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D000970:Antineoplastic Agents; D015820:Cadherins; D018121:Receptors, Cytokine; D010566:Virulence Factors, Bordetella; C555000:AMFR protein, human; C555002:Amfr protein, mouse; D060285:Receptors, Autocrine Motility Factor; D044767:Ubiquitin-Protein Ligases