Cell microenvironment and carcinogenesis in vivo and in vitro

Normal cells of many types are located in vivo and in vitro at the boundary between the two compartments of their microenvironment: between the noncellular surface (artificial substrates and cell-made matrices) and the humoral medium. Altered reactions to both these parts of microenvironment and to neighbouring cells are characteristic of neoplastic cells. Due to deficient spreading on the substrate and to decreased anchorage-dependence of growth, neoplastic cells become less demanding in their requirements for the noncellular substrate. These data obtained in vitro suggest that neoplastic cells in vivo may be less specific in their territorial requirements than are normal cells. Formation of promoting territories, that is, of boundaries between the humoral medium and abnormal non-cellular matrix, may play an important role in many types of carcinogenesis. In particular, capsules around implanted plastic films can be regarded as promoting territories for proliferation of neoplastic cells at the early stages of foreign body carcinogenesis. The role of local changes in tissue environment in carcinogenesis and, in particular, the importance of stromal factors, were advocated many years ago by such investigators as Ribbert, Fischer-Wasels, Bogomolez, Orr and others. The study of this problem is now gaining new momentum, due mainly to recent advances in the understanding of interactions of normal and neoplastic cells with their environment in cultures. In the first part of this communication I summarize briefly some conclusions obtained in studies in vitro. In the second part, I discuss the possible role of environmental changes in certain types of carcinogenesis in vivo, and especially in foreign body carcinogenesis.