Relay-Version: version B 2.10 5/3/83; site utzoo.UUCP Path: utzoo!mnetor!seismo!gatech!mit-eddie!ll-xn!ames!lll-tis!ptsfa!ihnp4!chinet!nucsrl!coray From: coray@nucsrl.UUCP (Elizabeth) Newsgroups: sci.research Subject: Re: cancer Message-ID: <3100001@nucsrl.UUCP> Date: Thu, 25-Jun-87 18:13:43 EDT Article-I.D.: nucsrl.3100001 Posted: Thu Jun 25 18:13:43 1987 Date-Received: Sun, 28-Jun-87 04:51:22 EDT References: <3414@ecsvax.UUCP> Organization: Northwestern U, Evanston IL, USA Lines: 69 I assume the holistic question is being asked because there is some element of desperation, looking for hope along any pathway. Actually, I think the hope lies along the lines of understanding the characteristics of malignant neoplastic cells at the functional level. Historically, most studies of the malignant phenotype have attempted to identify cancer-specific properties, i.e. properties common to all cancer cells, or to all cancer cells of a certain type, but absent in all normal cell types. However, heterogeneity of the properties of the cells in a malignant tumor is a well documented phenomenon. A review is presented by Heppner, 1984. Tumor heteogeneity constitutes a major obstacle to investigations of the pheotype of cancer cells. For this reason, it may not be possible to obtain a biochemical understanding of the pheonotype of cancer cells merely by comparing cancer cells with normal cells. A more accessible approach is based on the assumption that cancer cells can be characterized by possessing a certain combination of properties, each also present in normal cells. The typical properties of the cancer cells, such as their autonomous growth, their invasion into and degradation of normal tissue, and their metastasizing capacity, are all functions of normal cells. A variety of normal cells can effect tissue degradation. Explants of cancer tissue consistently cause proteolytic degradation of the plasma clots on which they are grown. More recently, it was found that release of plasminogen activators from on transformed culture cells induces a massive increase in extracellular proteolytic activity. Current research indicates that plasminogen activators, particularly a plasminogen activator of the urokinase type (u-PA), plays a role in tissue degradation. In particular, the cancer cell secretes a pro-u-PA, which undergoes a transofmation to u-PA, which activates plasminogen to form plasmin, and plasmin is capable of degrading the extracellular matrix. This proteolytic cascade provides a mechanism which explains tissue degradation. In addition, the cancer cell is capable of actually attaching to laminin, thereby allowing it to activate plasmin locally. In short, it would seem that there is a specific mechanism which explains invasiveness. Now, plasminogen activator could also be a nonspecific marker for tumors. If the immunoreactivity of the cancer cell to plasminogen activator is due to the fact that there is actually a receptor site which acts to bind the nonactive part of the plasminogen activator--thereby explaining both the cancer cells relative immunity to the action of plasmin, since the active site is directed away from the cells, and also explaining the cancer cells ability to apply plasminogen activation very locally, then a mechanism exists by which one can deliver a plasminogen "deactivator" to the cancer cell. One way to do this might be if one were able to construct a plasminogen "deactivator" bound to the inactive section of the plasminogen activator (in place of the active site). This plasminogen "deactivator" would then attach to the surface of the cancer cell and inhibit the effect of the pro-u-PA which the cell secretes. This last was entirely theoretical (never let a computer scientist study biochemistry), but it would seem to be a better way of combatting a specific mechanism than a holistic approach. How holistic approaches affect specific mechanisms is never very clear, but as an ex-cancer patient myself, I think it is better to be very well informed than to be hopeful in a general or holistic way. Cancer does not have to be fatal, there are advances being made immediately, and reality has alot more to offer than voodoo. I'd try Advances in Cancer Research to get a start. M.E. Corey "I don't know anything. I'm just a graduate student."