Biology of cancer; from cellular and molecular mechanisms to developmental processes and adaptation

• Published in: Seminars in cancer biology 2022-11, Vol.86 (Pt 3), p.600-615
• Main Author: Motofei, Ion G.
• Format: Article
• Language: English
• Subjects: adaptation; Biology; cancer; Cell Differentiation - genetics; cell-matrix integration; developmental processes; Extracellular Matrix; Humans; Neoplasms - genetics; Neoplasms - pathology; supracellular control of proliferation; Tumor Microenvironment - genetics
• ISSN: 1044-579X; 1096-3650
• DOI: 10.1016/j.semcancer.2021.10.003

•In multicellular organisms, there is a supracellular control of mitosis, both in health and in disease/cancer.•Structurally, supracellular control is composed of cells and extracellular matrix.•Functionally, supracellular control integrates genetic, systemic and environmental data, elaborating contextual instructions.•Such contextual instructions conduct mitosis and differentiation, which intervene in development and adaptation.•Understanding these processes and their aberrant evolution is an essential step in cancer prevention and therapy. Cancer research has been largely focused on the cellular and molecular levels of investigation. Recent data show that not only the cell but also the extracellular matrix plays a major role in the progression of malignancy. In this way, the cells and the extracellular matrix create a specific local microenvironment that supports malignant development. At the same time, cancer implies a systemic evolution which is closely related to developmental processes and adaptation. Consequently, there is currently a real gap between the local investigation of cancer at the microenvironmental level, and the pathophysiological approach to cancer as a systemic disease. In fact, the cells and the matrix are not only complementary structures but also interdependent components that act synergistically. Such relationships lead to cell-matrix integration, a supracellular form of biological organization that supports tissue development. The emergence of this supracellular level of organization, as a structure, leads to the emergence of the supracellular control of proliferation, as a supracellular function. In humans, proliferation is generally involved in developmental processes and adaptation. These processes suppose a specific configuration at the systemic level, which generates high-order guidance for local supracellular control of proliferation. In conclusion, the supracellular control of proliferation act as an interface between the downstream level of cell division and differentiation, and upstream level of developmental processes and adaptation. Understanding these processes and their disorders is useful not only to complete the big picture of malignancy as a systemic disease, but also to open new treatment perspectives in the form of etiopathogenic (supracellular or informational) therapies.