Spontaneous Phenotypic Shifts from Low to High Metastatic Capacity
Tumor progression from low to high malignancy is believed to occur in multiple steps (1). Analogous to mutation/selection the process of tumor progression is thought to have its basis in the continuous emergence of successive clones of tumor cell variants, one gradually replacing another, through the intervention of natural or artificial selection pressures (2). Highly malignant metastasizing tumor cells have been shown to differ from low malignant non-metastasizing ones in a number of properties such as plasma membrane enzyme activities (3), cell surface antigen shedding (4), tumor antigenicity and immunogenicity (5). A critical question is whether all these specific properties have been accumulated in the metastatic cell in a stepwise fashion. Is each new property the result of a process of random variation and host selection? How can a random process result in the generation of cells endowed with not just one but a number of very specific properties that enable them to cross the various biological barriers of the host, to survive and grow in different microenvironments?
KeywordsTumor Antigen Tumor Line Tumor Variant Metastasize Tumor Cell High Malignancy
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