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Malignant transformation of human fibroblasts correlates with increased activity of receptor-bound plasminogen activator.
Cancer Res. 1991 Feb 15; 51(4):1221-6.CR

Abstract

To determine whether a relationship exists among urokinase plasminogen activator (u-PA) activity, tissue plasminogen activator (t-PA) activity, and the malignant transformation of human fibroblasts, we measured receptor-bound and secreted u-PAs and t-PA activity in fibroblast cell strains of a unique cell lineage and compared the results with the values obtained in human fibrosarcoma-derived cell lines and control cell lines. The lineage consists of four nonmalignant, infinite life span cell strains, clonally derived from a finite life span, neonatal foreskin-derived cell line or one of its derivatives and 10 malignant cell strains clonally derived from that same derivative. Seven of the latter were malignantly transformed by K-, H-, or N-ras oncogene transfection, two were obtained following carcinogen treatment, and one arose spontaneously. All 10 malignant strains in this lineage exhibited significantly higher levels of activity of receptor-bound u-PA than was found in the cell strain from which they arose or the nonmalignant cell strains derived from it. The ras oncogene-transformed malignant strains also exhibited significantly higher levels of activity of receptor-bound t-PA than their cell strain of origin. The other three malignant strains showed undetectable levels, consistent with their attaining the malignant state by an alternate process. The five fully malignant fibrosarcoma-derived cell lines tested also showed high levels of receptor-bound u-PA and t-PA. The majority (greater than or equal to 80%) of the nonmalignant control cell lines did not do so. The 10 malignant cell strains in the lineage also exhibited higher levels of activity of secreted high molecular weight u-PA or t-PA than did their cell strain of origin and the nonmalignant cell strains derived from it, as did the malignant fibrosarcoma-derived cell lines. The data suggest that the malignant state of human fibroblasts is always associated with high levels of activity of receptor-bound u-PA, and in addition cells transformed to the malignant state are very likely to exhibit high levels of receptor-bound t-PA and secreted forms of plasminogen activators.

Authors+Show Affiliations

Department of Microbiology, Michigan State University, East Lansing 48824-1316.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

1847659

Citation

Jankun, J, et al. "Malignant Transformation of Human Fibroblasts Correlates With Increased Activity of Receptor-bound Plasminogen Activator." Cancer Research, vol. 51, no. 4, 1991, pp. 1221-6.
Jankun J, Maher VM, McCormick JJ. Malignant transformation of human fibroblasts correlates with increased activity of receptor-bound plasminogen activator. Cancer Res. 1991;51(4):1221-6.
Jankun, J., Maher, V. M., & McCormick, J. J. (1991). Malignant transformation of human fibroblasts correlates with increased activity of receptor-bound plasminogen activator. Cancer Research, 51(4), 1221-6.
Jankun J, Maher VM, McCormick JJ. Malignant Transformation of Human Fibroblasts Correlates With Increased Activity of Receptor-bound Plasminogen Activator. Cancer Res. 1991 Feb 15;51(4):1221-6. PubMed PMID: 1847659.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Malignant transformation of human fibroblasts correlates with increased activity of receptor-bound plasminogen activator. AU - Jankun,J, AU - Maher,V M, AU - McCormick,J J, PY - 1991/2/15/pubmed PY - 1991/2/15/medline PY - 1991/2/15/entrez SP - 1221 EP - 6 JF - Cancer research JO - Cancer Res VL - 51 IS - 4 N2 - To determine whether a relationship exists among urokinase plasminogen activator (u-PA) activity, tissue plasminogen activator (t-PA) activity, and the malignant transformation of human fibroblasts, we measured receptor-bound and secreted u-PAs and t-PA activity in fibroblast cell strains of a unique cell lineage and compared the results with the values obtained in human fibrosarcoma-derived cell lines and control cell lines. The lineage consists of four nonmalignant, infinite life span cell strains, clonally derived from a finite life span, neonatal foreskin-derived cell line or one of its derivatives and 10 malignant cell strains clonally derived from that same derivative. Seven of the latter were malignantly transformed by K-, H-, or N-ras oncogene transfection, two were obtained following carcinogen treatment, and one arose spontaneously. All 10 malignant strains in this lineage exhibited significantly higher levels of activity of receptor-bound u-PA than was found in the cell strain from which they arose or the nonmalignant cell strains derived from it. The ras oncogene-transformed malignant strains also exhibited significantly higher levels of activity of receptor-bound t-PA than their cell strain of origin. The other three malignant strains showed undetectable levels, consistent with their attaining the malignant state by an alternate process. The five fully malignant fibrosarcoma-derived cell lines tested also showed high levels of receptor-bound u-PA and t-PA. The majority (greater than or equal to 80%) of the nonmalignant control cell lines did not do so. The 10 malignant cell strains in the lineage also exhibited higher levels of activity of secreted high molecular weight u-PA or t-PA than did their cell strain of origin and the nonmalignant cell strains derived from it, as did the malignant fibrosarcoma-derived cell lines. The data suggest that the malignant state of human fibroblasts is always associated with high levels of activity of receptor-bound u-PA, and in addition cells transformed to the malignant state are very likely to exhibit high levels of receptor-bound t-PA and secreted forms of plasminogen activators. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/1847659/Malignant_transformation_of_human_fibroblasts_correlates_with_increased_activity_of_receptor_bound_plasminogen_activator_ DB - PRIME DP - Unbound Medicine ER -