Implication of direct host-tumor intercellular interactions in non-immune host resistance to neoplastic growth

The hallmark of cancer as a disease is impaired homeostasis, which in normal tissue is maintained by the network of direct intercellular contacts. The cell-cell interaction machinery consists of intercellular junctions of various types, each of which has a role in the control of cell growth, differentiation, and motility. In cancer, the function of intercellular junctions is altered, often at quite advanced stages of tumor progression, while proper intercellular interactions between normal and tumor cells may control and even suppress, otherwise, aberrant growth and behavior of neoplastic cells. This type of host resistance to neoplastic growth implies a homotypic functional partnership between tumor cells and their normal host counterparts and, thus, is to a certain extent complementary to immune defense against tumorigenesis, which is effective only when tumor cells became 'foreign' for the host. Functional interactions between host and tumor cells could be lost at different stages of tumorigenesis through a range of mechanisms. In some cases, host-tumor interactions may be impaired reversibly, which in turn gives rise to the possibility of restoring this component of host defense against cancer by correctional interventions. This review highlights the role that direct intercellular host-tumor interactions may play in natural host resistance against neoplastic growth, with an emphasis on the underlying mechanisms of both their function and impairment.