CELL FUSION AND THE GENERATION OF TUMOR DIVERSITY

Project Details

Description

The generation of diversity is a hallmark of the malignant process. This
diversity results in the observed heterogeneity in tumor cell properties,
the acquisition of metastatic capacity and the development of resistance to
treatment. Diversity could be the result of accumulated, random point
mutations and cell selection. An alternative, which has recently gained in
experimental support, is that tumor diversity is promoted through cell-cell
fusion and chromosome selection. The goal of our study is to extend these
findings and critically assess the contribution of cell fusion to tumor
development and progression using sensitive, unambiguous and nonselective
markers for fusion events. This will be accomplished by analysis of the
formation of heteropolymers of autosomal, multimeric alloisozymes in
tumor-bearing allophenic (tetraparental, chimeric) mice. The results
obtained will be independent of host cell contamination, can be analyzed on
a tissue or individual cell basis, and will be free of histocompatibility
effects or selection. Appropriate marker enzymes are available
representative of different chromosomes, including glucose phosphate
isomerase, malate dehydrogenase, phosphoglucomutase, isocitrate
dehydrogenase and autosomal glucose-6-phosphate dehydrogenase. The primary
tumor system to be employed is the methylcholanthrene-induced sarcoma.
Using this system, the aims of our study are to determine the contribution
of cell fusion to tumor development, to metastatic progression and to the
acquisition of resistance to therapy, and to identify the cell partner for
tumor fusion events. The results of these studies could provide greater
insight into the pathogenesis of malignancy and the mechanisms by which
tumors respond to their environment.
StatusFinished
Effective start/end date8/1/8611/30/89

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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