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Metastatic dissemination of 3LL variants after treatment with monoclonal antibody to a tumor-associated antigen
Authors:Ada Sacchi  Stephen Kennel Jr  Pier Giorgio Natali  Giulio Tibursi  Cinzia Apollonj Ghetti
Affiliation:(1) Istituto Regina Elena per to studio e la cura dei tumori, Roma, Italy;(2) Laboratorio Biofisica, Roma, Italy;(3) Laboratorio Immunologia, Roma, Italy;(4) Biologia Cellulare, Università "lsquo"La Sapienza"rsquo", Roma, Italy;(5) Biology Division, Oak Ridge National Laboratory, 37831 Tennessee, U.S.A.
Abstract:Two tumor lines derived from 3LL (Lewis lung carcinoma) endowed with different metastatic potential and stable for their metastatic phenotype during serial in vivo passages, have been analysed for growth and dissemination following treatment with a monoclonal antibody. We have used a recently developed MoAb 135-13C to a tumor-associated antigen of murine lung carcinoma having an apparent molecular weight of 180000 (TSP-180). The metastatic dissemination of the 3LL variants before and after treatment with the MoAb has been correlated with the expression on the cell surface of the MHC antigens (Db, Kb) and of the TSP-180 protein. The results of this study indicate that cell with high TSP-180 protein expression and MHC antigen expression have the greatest metastatic potential. Administration of MoAb 135-13C to tumor-bearing mice or i.v. injection of cells preincubated with the MoAb 135-13C increase the dissemination capacity of the variant endowed with lower metastatic potential while inducing a reverse effect on the high metastatic one. Studies on the MHC expression demonstrate that MoAb 135-13C treatment induces changes in the Db and Kb expression at level of secondary neoplasms. The results are discussed in view of the importance of the use of the metastatic variants to study therapeutic effect of specific targeting agent.
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