Antiproliferative and antitumor effects of α-interferon in renal cell carcinomas: Correlation with the expression of a kidney-associated differentiation glycoprotein Journal Article
| Authors: | Nanus, D. M.; Pfeffer, L. M.; Bander, N. H.; Bahri, S.; Albino, A. P. |
| Article Title: | Antiproliferative and antitumor effects of α-interferon in renal cell carcinomas: Correlation with the expression of a kidney-associated differentiation glycoprotein |
| Abstract: | Human leukocyte α-interferon (IFN-a) has significant antitumor activity in advanced renal cell carcinoma (RC), with approximately 15% (range, 5 to 29%) of patients subjected to IFN-a therapy exhibiting a major objective response. We assayed 16 RC cell lines for intrinsic sensitivity to the growth-inhibitory effects of recombinant IFN-a. Similar to results observed in patients, cultured RCs could be divided into those that are inhibited by IFN-a and those that are not. In addition, the IFN-α-sensitive or -resistant phenotype of cultured RCs was correlated with surface expression of six unrelated kidney-associated differentiation antigens. The expression of one antigen, a Mr 160,000 glycoprotein (gpl60), was found to correlate with resistance to IFN-a. Proliferation of seven RC cell lines expressing gp 160 (gpl60+) was not significantly inhibited by IFN-a at concentrations as high as 3000 units/ml. In contrast, proliferation of eight of nine RC cell lines lacking expression of gpl60 (gpl60~) was markedly inhibited by IFN-a. The effect of IFN-a on gpl60+ and gpl60− RC xenografts in nu/nu mice was examined. In separate experiments, two gpl60+ RC cell lines and five gpl60− RC cell lines were injected s.c. into nu/nu mice; one half of the mice were subsequently treated with 106 units of IFN-a i.p. 3 times a wk, and one half received no IFN-a. Tumors appeared at the sites of inoculation in all mice given injections of gpl60+ RC cell lines within 10 to 25 days regardless of INF-a therapy. Mice given injections ofgpl60~ RC cell lines, but not receiving IFN-a, also formed tumors. In contrast, gpl60− RC cell lines injected into mice that were treated with IFN-a exhibited a marked sensitivity, as demonstrated by either no tumor formation or delayed tumor formation. We conclude that the absence of gpl60 expression by RCs may be predictive of sensitivity to the antitumor effects of IFN-a and, thus, provide a basis for identifying IFN–responsive patients. © 1990, American Association for Cancer Research. All rights reserved. |
| Keywords: | human cell; nonhuman; alpha interferon; antigen expression; mouse; animal; mice; cell division; tumor differentiation; cell line; animal experiment; antineoplastic activity; tumor cells, cultured; kidney carcinoma; kidney neoplasms; antibodies, monoclonal; cell culture; carcinoma, renal cell; mice, nude; tumor cell line; transplantation, heterologous; radioisotope; glycoproteins; glycoprotein; antigens, differentiation; kidney tubules, proximal; interferon type i, recombinant; human; female; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s. |
| Journal Title: | Cancer Research |
| Volume: | 50 |
| Issue: | 14 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 1990-07-15 |
| Start Page: | 4190 |
| End Page: | 4194 |
| Language: | English |
| PUBMED: | 2364374 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 27 January 2020 -- Source: Scopus |
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