Cell Growth & Differentiation, Vol 3, Issue 3 191-197, Copyright © 1992 by American Association of Cancer Research
Complex expression of the genes coding for plasminogen activators and their inhibitors in HeLa-smooth muscle cell hybrids
WE Laug, XR Cao, A T'Ang, S Pasquale, R Mundy, M Coensgen-Luna and B Weissman
Division of Hematology-Oncology, Childrens Hospital of Los Angeles, California.
As cells progress through the multistep process of neoplastic
transformation, they eventually acquire the property of invasive behavior.
Although both plasminogen activators (PA) and their inhibitors (PAI)
contribute to this process, their regulation in normal and transformed
cells remains poorly defined. Because somatic cell hybrids provide useful
tools for examining the transformation pathway, tumorigenic and invasive
HeLa cells were fused with human normal vascular smooth muscle cells and
tested for invasion-related parameters, including the expression of PA and
PAI genes, and matrix degradation. Both parental cell lines produced large
amounts of PAI activities with no detectable PA in either cellular or
secreted form. Opposite findings were obtained with the hybrid cell lines,
which demonstrated the presence of receptor-bound and secreted PA but
absence of enzymatically measurable PAI activities. Both urokinase-type and
tissue-type PA were found in cell-associated and secreted form in the
hybrid cells. In addition, expression of the urokinase-type PA receptor
gene was found in the three hybrid cells and the vascular smooth muscle
cells but not in the HeLa cells. Expression of active, receptor-bound and
secreted PA provided the nontumorigenic hybrid cells with the enzymatic
tools to degrade extracellular proteins in a plasminogen-dependent manner.
Thus, the hybrid cells lost tumorigenicity while retaining the
tissue-degrading capability of HeLa cells. These hybrid cell lines should
prove to be important reagents for investigating the complex regulatory
control of PA and PAI gene expression.