Cellular heterogeneity in malignant tumors

摘要

The concept of tumor progression was introduced by Foulds (1954) who stated that tumor progression is a process of independent, stepwise and permanent changes in one or more different properties of a malignant tumor. This implies that a tumor cannot simply be a homogeneous population of malignant cells. The process of progression is thought to result from genetic instability of the tumor cells leading to a continous emergence of successive clones of tumor cell variants, one gradually replacing another, through the intervention of natural or artificial selection pressures (Cairns, 1975; Nowell, 1976; Nowell, 1986). The result is increasingly genotypically and pheno-typically abnormal subpopulations. Local microenvironmental conditions may affect the ability of variant sublines to survive and proliferate. Thus, clonal evolution of neoplastic cells may be the underlying mechanism of tumor cell heterogeneity in malignant tumors (Nowell, 1916; Fialkow, 1976). Antigen expression, immunogenic specificity, karyotype, DNA content, degree of cellular differentiation (morphology), growth characteristics, biochemical expression, drug sensitivity, hormone-dependency and metastatic potential are some of the characteristics which can change as a tumor develops resulting in alteration of tumor behaviour and cellular heterogeneity (Dexter and Calabresi, 1982). This process is a fundamental property of cancer and has important biological and clinical consequences among which augmentation of tumor progression and development of resistance to treatment are the most crucial for the host (Schnipper, 1986).