Properties of plasminogen activators formed by neoplastic human cell cultures

Our plain-English summary of Properties of plasminogen activators formed by neoplastic human cell cultures, by D.B. Rifkin, J.N. Loeb, G. Moore, et al (The Journal of Experimental Medicine, 1974).

The study

• Authors: D.B. Rifkin, J.N. Loeb, G. Moore, E. Reich
• Journal: The Journal of Experimental Medicine
• Published: 1974;139(5):1317-28
• Cited by: 198 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

A series of human cell lines has been examined for fibrinolysis in culture. The sera that are activating for fibrinolysis by human cells are mouse, monkey, human, horse, and bovine. Individual human sera show considerable variation in the ability to activate fibrinolysis. In common with other neoplastic or transformed mammalian and avian cell cultures, human cell lines of neoplastic origin produce substantial amounts of plasminogen activator. Several cultures of nonmalignant origin also produce plasminogen activator, whereas cultures obtained from trypsinized human embryos, or from human embryonic skin do not. The human melanoma plasminogen activators are of two kinds: a major component with a mol wt of 50,000, and a minor species with a mol wt of approximately 60,000. Both are DFP sensitive, serine proteases.

In plain English

This 1974 laboratory study tested whether human tumor cells grown in culture release a plasminogen activator. This enzyme works with plasminogen, a protein in blood serum, to break down fibrin, the protein in blood clots. The authors studied three human tumor cell lines, from an osteosarcoma, a mesothelioma (RPMI-212) and a malignant melanoma, and several human embryonic cultures of nonmalignant origin. The article does not discuss asbestos. Fluid from all three tumor lines broke down fibrin when mixed with suitable sera, such as monkey, mouse, human, bovine and horse. The mesothelioma cells made significantly less activator than the other two lines: 2-10 pM, against 20-200 pM for melanoma. In melanoma fluid the activator had a major form of molecular weight 48,000 and a minor form of about 60,000, both serine proteases. Embryonic fibroblasts and skin cells showed no significant activity. Embryonic lung cells showed high activity, partly serum-independent. Sera from more than 100 people varied about 30-fold. The authors concluded that fibrinolytic activity is likely associated with at least some human malignancies. They cautioned that their findings came from established cell lines.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) cell-culture study of enzyme activity released by human cell lines
• Who was studied: Three human tumor cell lines: an osteosarcoma (RPMI-41), a mesothelioma (RPMI-212) and a malignant melanoma (RPMI-8352). Also human embryonic cell cultures of nonmalignant origin (fibroblasts, skin, lung, kidney) and sera from more than 100 individuals. The site of the mesothelioma is not stated.
• Exposure: No asbestos or other fiber exposure was studied. The study measured fibrin breakdown by fluid from the cultured cells when mixed with sera from various animal species and from individual humans.
• Main results:
  • Fluid (conditioned medium) from each of the three tumor cell lines broke down fibrin when combined with appropriate sera.
  • For the human tumor cell lines, monkey, mouse, human, bovine and horse sera were activating. Rat, fetal bovine, dog and fetal pig sera were not.
  • The mesothelioma cultures produced significantly less activator than the osteosarcoma and melanoma lines.
  • Estimated activator concentration was 2-10 pM in mesothelioma-conditioned medium, compared with 10-30 pM in transformed chick cultures.
  • Estimated activator concentration in melanoma-conditioned medium was 20-200 pM.
  • Partially purified melanoma cell factor contained a major component of molecular weight 48,000 and a minor component of approximately 60,000.
  • Both melanoma activator components were sensitive to DFP and were serine proteases.
  • Among nonmalignant cultures, fibroblasts from trypsinized embryos and embryonic skin cells showed no significant fibrinolytic activity.
  • The embryonic kidney cell line showed no activity, which the authors had not expected.
  • Embryonic lung cells produced high fibrinolysis, but some of it did not depend on serum.
  • Sera from more than 100 individuals varied widely: the most active serum was about 30-fold more active than the least active.
  • No distinctive pattern of serum activity had been linked to any category of disease.
• The authors' conclusion: The authors concluded that the human tumor cell enzyme resembles those from neoplastic and transformed cultures of other species. Together with clinical observations, this suggested to them that fibrinolytic activity is likely to be associated with at least some human malignancies.
• Limitations the authors state:
  • The findings rest on established cell lines, some kept in culture for years. Establishing cell lines may favor variants that produce the activator.
  • A firm link between fibrinolysis and human neoplasia would require study of larger numbers of cell lines, transformants and primary cultures from surgical specimens.
  • High plasminogen activator levels cannot be taken as diagnostic of cancer, because some nonmalignant cells also produce them.

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