Production of plasminogen activator by a primary HSV-2-induced hamster fibrosarcoma and itsin vivo derived sublines

Abstract

The plasminogen activator (PA) content of a primary HSV-2-induced hamster fibrosarcoma and sublines derived from its in vivo metastases was investigated using the indirect 125I-labeled fibrin plate method. Fresh tissue culture lines established from primary HSV-2-333-2-26 tumors were shown to produce levels of PA similar to sublines derived from lung or kidney foci that developed after resection of primary tumors. In comparison, normal hamster embryo fibroblast (NHEF) and baby hamster kidney cells produced little or no PA, although baby hamster lung fibroblasts produced intermediate levels of PA. In addition, no correlation was found between PA levels of the sublines and their ability to metastasize from subcutaneous tumors, although tumor cell lines were shown to produce significantly more PA than normal cells.

Modulation of type IV collagenase and plasminogen activator in a hamster fibrosarcoma by basement membrane components and lung fibroblasts

“…Attachment to the basement membrane is a prerequisite to dissolution of the extracellular matrix (Liotta et al, 1977) and experiments performed in vitro have demonstrated tumour cell binding to the basement membrane using laminin as the attachment factor (Terranova et al, 1982). We have, therefore, assessed the influence of BM components, and lung fibroblasts, on the secretion of type IV collagenase in sublines and clone of defined metastatic ability in the hamster tumour model (Walker et al, 1982;Teale et al, 1983Teale et al, ,1984Khidair et al, 1986). The secretion of plasminogen activator (PA), a serine protease capable of degrading serum plasminogen converting it to plasmin, which in turn is capable of degrading fibrin and laminin (Carlson et al, 1984;Liotta et al, 1981), was also investigated in this system.…”

“…PA induces the activation of plasminogen giving rise to plasmin which has been associated with the ability of tumour cells to metastasize (Carlson et al, 1984;Wang et al, 1980) possibility by its ability to degrade laminin (Liotta et al, 1981). We have previously shown that the hamster tumour cell lines used here are able to recrete PA but no correlation between the level of PA secretion and the metastatic profile was found (Khidair et al, 1986). We are now able to report that the addition of laminin, fibronectin or type IV collagen to the tumour cell lines failed to alter the expression of plasminogen activator activity.…”

“…Clones S4A and S9E were obtained following double cloning of the parental cell line by the limiting dilution method . Some of the characteristics of the in vivo and in vitro derived cell lines have been reported previously (Walker et al, 1982;Teale et al, 1983Teale et al, ,1984Khidair et al, 1986) and are summarised in Table I.…”

“…Media that had not been incubated with cells were incubated with plasminogen and used as control, to exclude any spontaneous release of radioactivity from the labelled plates. PA activity of the hamster fibrosarcoma cell lines has previously been shown to be of a secreted form and not cell bound (Khidair et al, 1986).…”