The propensity of tumor cells to spread in the body and produce metastases is the major cause of death from cancer. Recognition and adhesion among circulating tumor cells and between tumor and normal host cells leads to the formation of multicell emboli, a process directly related to the production of metastases. For this reason, understanding of the molecular mechanisms responsible for the in vivo aggregation and adhesion of malignant cells is important. The nature of the cell surface molecules that mediate such processes is beginning to be unravelled. Among them is a group of molecules capable of binding specific mono- and oligosaccharides and known as endogenous lectins. Previously, it was found that several human and rodent tumor cells contain cell surface and cytoplasmic galactoside-specific lectins. The molecular nature of the B16 melanoma lectin was characterized and monoclonal antibodies to endogenous lectin were developed as well as nono-specific polyclonal antibodies. Recently, it has been found that the presence of a lectin on the surface may be relate to neoplastic transformation and progression towards metastasis.
The aim of this project is to determine directly the role of tumor cell surface lectin in vitro (aggregation, adhesion) and in vivo (hematogenous spread). In particular, we suggest the following: 1. Determine the relation between the surface and cytoplasmic endogenous tumor cell lectin and the turnover rates. 2. Determine the degree of sequence homology among lectins isolated from different tumor systems. 3. Determine the ability of mono- and polyclonal antibodies or Fab' fragments to alter unique organophilic implantation of circulating tumor cells. 4. Identify and clone the gene(s) coding for tumor cell surface lectin, prepare specific cDNA probes and use them to identify genes in other tumor cell systems. 5. Transfect with lectin-specific genomic clone, cell variants from the recently derived angiosarcoma tumor system (BALB/c-A31) deficient in cell surface lectin and determine the appearance of the cell surface gene product. This will enable a direct comparison of the amount of the newly synthesized lectin with its expression at the cell surface of the other lectin-expressing cell variants of this tumor system in relation to growth properties in vitro and in vivo. It is expected that such studies will allow a critical evaluation of the role of tumor cell surface lectin in the various intercellular interactions which are relevant to the metastatic spread.
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