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ROLE OF PROTEINASES IN CELLULAR INVASION AND METASTASIS OF L1210 AND L5178Y MURINE LEUKEMIAS

The proteinase activities of the L1210 and L5178Y murine lymphocytic leukemias have been measured and characterized in order to determine whether a correlation exists between proteinase activity and metastatic potential. Such a correlation would be expected if proteinases promote invasion and metastasis by degrading host tissue. These lines were chosen for study because they are very similar in most respects, but differ dramatically in their ability to metastasize. The kinetics of tumor cell proliferation, death, and metastasis for these lines are the best currently available. / Tumor cell suspensions and supernatants were assayed for activity against basement membrane, elastin, Type I collagen, hemoglobin, casein, benzoyl-Arg-napthylamide, and N-acetyl-(Ala)(,3)-p-nitroanilide. Since no quantitative assay for the hydrolysis of intact basement membranes existed prior to these studies, a sensitive new one based on the hydrolysis of bovine lens capsule membranes has been developed. Significant levels of proteinase activities were detected in suspensions of both tumor lines against all the substrates tested, and it is clear that the spectrum of activities found is capable of facilitating metastasis. Two membrane-associated proteinases have been found in both tumor lines, one active against both basement membranes and benzoyl-Arg-napthylamide and the other against N-acetyl-(Ala)(,3)-p-nitroanilide. Host cells were primarily responsible for the hydrolysis of the other substrates, although there was some cathepsin D activity attributable to tumor cell death. / No significant differences in proteinase activity levels were detected between the two lines. hence, while these proteinase activities may assist in the metastasis of these two cell lines, some other factor must also be involved. The ability of the two tumor lines to bind to intact basement membranes was examined and no differences in binding capacity were detected. Thus, some other additional factor, such as the capacity for directional motility, is probably involved. / Source: Dissertation Abstracts International, Volume: 45-06, Section: B, page: 1662. / Thesis (Ph.D.)--The Florida State University, 1984.

Identiferoai:union.ndltd.org:fsu.edu/oai:fsu.digital.flvc.org:fsu_75347
ContributorsSMITH, CARR JOSEPH., Florida State University
Source SetsFlorida State University
Detected LanguageEnglish
TypeText
Format192 p.
RightsOn campus use only.
RelationDissertation Abstracts International

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