ISSN:
1573-7276
Keywords:
extravasation
;
fibronectin
;
integrin a5b1
;
lung colonization
;
metastasis
;
mice
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract The integrin α5β1 seems to be the most relevant receptor of tumor cells for binding to fibronectin. Although numerous studies suggest a role of tumor cell fibronectin interaction in tumor metastasis, differential integrin expression on tumor cells has, however, not been correlated with metastatic capabilities. We addressed this question by transfection of the integrin α5β1 cDNA into HT-29 human colon carcinoma cells which led to de novo expression of functional integrin α5β1. Similar to other reports, expression of the integrin α5β1 in HT-29 tumor cells exerted an inhibitory action on cell proliferation as indicated in our study by formation of fewer colonies in soft agar. The tumor growth inhibitory property of the integrin α5β1 was also shown by reduction of subcutaneous xenograft growth in nude mice to approximately 50% of that of control transfectants. For the first time, we found that several clones of integrin α5 subunit transfectants displayed dramatically reduced formation of lung colonies and cutaneous metastasis after intravenous injec-tion into nude mice. While most animals inoculated with control transfectant cells formed macroscopically visible lung colonies ranging from 12.6 ± 2.6 to 22.0 ± 6.6 (mean colony number ± SEM), mice inoculated with HT-29 cell clones expressing the integrin a5b1 were almost completely free of lung colonies (ranging from 0.0 ± 0 to 0.2 ± 0.1). Our results imply that integrin α5β1 expression inhibits circulating tumor cells in pursuing late steps of the metastatic process as represented by the artificial metastasis (lung colonisation) model. © Rapid Science Ltd.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1006581424490
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