Effects of tissue culture environment on growth patterns and ultrastructure of poorly differentiated human cervical...

Growth patterns and ultrastructure were compared between biopsy specimens and primary cultures of poorly differentiated carcinomas of the human uterine cervix. Though not obvious histologically, all carcinomas in vivo retained ultrastructural traits of squamous, glandular, or basal cell differentiation. Carcinomas with squamous traits grew as compact masses in vivo and formed cohesive colonies in vitro; tumors with basal and glandular traits infiltrated host tissues in a dispersed fashion, but their growth patterns in vitro were variable and unpredictable. The growth patterns of mixed carcinomas, in which squamous and glandular characteristics were evident in the same cells, generally resembled those of tumors with squamous traits. The levels of differentiation in vitro exceeded those found in vivo: Tonofilaments, desmosomes, and glycogen aggregations (squamous traits) as well as secretory vesicles, endoplasmic reticulum, and cilia (grandular traits) became more numerous and complex in culture. The direction of differentiation, expressed in vivo, usually persisted in vitro, through squamous traits appeared de novo or became more prominent when some of the tumors were explanted. The enhancement of differentiation by the culture environment indicated that the cervical carcinomas did not express their full potential to differentiate when growing in the natural host. The coexistence of squamous and glandular traits in the same cells and the capacity of tumors to shift from a glandular to a squamous differentiative pathway upon explantation support the concept that cervical carcinomas originate in bipotential cells, i.e, either reserve cells or metaplastic basal cells derived from the glandular epithelium.