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Titolo:
Loss of differentiation of 4NQO-induced rat malignant oral keratinocytes correlates with metastatic dissemination and is associated with a reduced cellular response to TGF-beta 1 and an altered receptor profile
Autore:
Davies, M; Paterson, IC; Stone, A; Huntley, S; Patel, V; Curtis, R; Matthews, JB; Pring, M; Eveson, JW; Prime, SS;
Indirizzi:
Univ Bristol, Dept Oral & Dent Sci, Div Oral Med Pathol & Microbiol, Bristol, Avon, England Univ Bristol Bristol Avon England ol & Microbiol, Bristol, Avon, England NIH, Cellular Dev & Oncol Lab, Bethesda, MD 20892 USA NIH Bethesda MD USA20892 ellular Dev & Oncol Lab, Bethesda, MD 20892 USA Millennium Pharmaceut, Cambridge, MA USA Millennium Pharmaceut Cambridge MA USA ium Pharmaceut, Cambridge, MA USA Univ Birmingham, Dept Oral Pathol, Birmingham, W Midlands, England Univ Birmingham Birmingham W Midlands England ngham, W Midlands, England
Titolo Testata:
JOURNAL OF ORAL PATHOLOGY & MEDICINE
fascicolo: 9, volume: 28, anno: 1999,
pagine: 397 - 405
SICI:
0904-2512(199910)28:9<397:LODO4R>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
GROWTH-FACTOR-BETA; BENIGN SKIN TUMORS; MOUSE SKIN; TRANSFORMING GROWTH-FACTOR-BETA-1; IN-VITRO; SPINDLE CARCINOMAS; EPITHELIAL-CELLS; HIGH-RISK; EXPRESSION; PROGRESSION;
Keywords:
differentiation; keratinocytes; metastases; TGF-beta;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Prime, SS Univ Bristol, Bristol Dent Hosp & Sch, Div Oral Med Pathol & Microbiol, Lower Maudlin St, Bristol BS1 2LY, Avon, England Univ Bristol LowerMaudlin St Bristol Avon England BS1 2LY gland
Citazione:
M. Davies et al., "Loss of differentiation of 4NQO-induced rat malignant oral keratinocytes correlates with metastatic dissemination and is associated with a reduced cellular response to TGF-beta 1 and an altered receptor profile", J ORAL PATH, 28(9), 1999, pp. 397-405

Abstract

This study examined the metastatic capacity of clonal populations of 4NQO-induced rat malignant oral keratinocytes following orthotopic transplantation to athymic mice. Polygonal and spindle cells formed well-differentiated squamous cell carcinomas (keratin positive and vimentin negative) and undifferentiated spindle cell tumours (keratin negative and vimentin positive), respectively, in almost 100% of animals at the site of inoculation (floor of mouth). Transplantation of 5x10(6) cells of either cell type at high celldensity resulted in approximately 50% of animals forming pulmonary metastases. By contrast, inoculation of 2x10(6) differentiated polygonal cells resulted in the formation of significantly fewer pulmonary metastases than theundifferentiated spindle cells. A single well-differentiated clone of polygonal cells and 3 of 4 of the undifferentiated spindle cell lines produced comparable levels of TGF-beta 1. One undifferentiated spindle cell line expressed significantly more TGF-beta 1 and, following transplantation orthotopically, fewer animals formed pulmonary metastases despite the formation ofprimary tumours in almost all grafted animals, suggesting that TGF-beta 1 can act as a tumour suppressor in this cell type. All cell lines produced comparable amounts of TGF-beta 2. The clones of polygonal cells were markedly inhibited and the spindle cells were only partially inhibited by exogenous TGF-beta 1. Both cell types expressed high-affinity TGF-beta cell surfacereceptors; the ratio of type I to type II TGF-beta receptors was 1.0:<3.0 in the spindle cells and 1.0:17.9 in the polygonal clone. The results suggest that differentiated rat malignant oral keratinocytes are less aggressiveand have a decreased potential to metastasise than their undifferentiated spindle cell counterparts. This may be attributable, in part, to a change in TGF-beta receptor profile leading to the partial loss of response to exogenous TGF-beta 1.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/01/21 alle ore 10:08:54