Med Hypotheses. 1985 Mar;16(3):303-13.
Congenital neoplasia--a stem cell pathology.
The theory presented herewith provides a unified explanation for neoplasia and teratogenesis, both regarded here as stem cell disorders. Proliferating cells in the organism form two mutually exclusive classes, immortal stem cells and transitional cells whose life span is limited. Any lasting change in the organism e.g. tissue differentiation or neoplasia, is determined by stem cells. Congenital as well as adult neoplasms exhibit three key features: maturation arrest, stem cell pool expansion and increased cell turnover and they progress through the following states: dysplasia, neoplasia in situ, benign stage (e.g. polyp) and overt neoplasia. The neoplasm is regarded here as an organ with a purpose intended to supply the organism with a missing substance. Besides serving as tissue progenitors, stem cells are postulated here to secrete a substance 'A' necessary for a proper tissue function. Carcinogens interfere with the substance production mainly by depleting stem cells so that less 'A' is produced. The capacity of the adult to replenish the depleted stem cells is limited, and the missing substance has to be formed by an alternative way i.e. by Neoplasia. The 'A' substitute formed by the neoplasm denominated as 'B' is however less efficient than 'A'. Neoplastic growth thus depends upon the relative abundance of substances 'A' and 'B'. Since in the growing organism, stem cells multiply, some of the missing 'A' is replenished by them and the neoplasm may regress.