Ordered heterogeneity and its decline in cancer and aging

Area of Science:

• Developmental Biology
• Cell Biology
• Cancer Biology

Background:

• Ordered heterogeneity was established as a fundamental characteristic of living organisms.
• The principle "order in the large over heterogeneity in the small" guides the theory of organisms.
• Numerous examples now confirm the broad applicability of ordered heterogeneity.

Purpose of the Study:

• To review and synthesize examples of ordered heterogeneity in biological systems.
• To evaluate the role of the plasma membrane and adhesion molecules in this phenomenon.
• To demonstrate how ordered heterogeneity provides a unifying framework for understanding normal and neoplastic development.

Main Methods:

• Review of established biological principles and examples.
• Analysis of cell behavior in embryological development, tissue reaggregation, and cell proliferation.
• Examination of cell growth heterogeneity in aging and tumors.
• Investigation of contact-induced normalization of initiated cells in epidermal and liver systems.

Main Results:

• Ordered heterogeneity is evident in embryological development, cell sorting, and contact inhibition of proliferation.
• Carcinogen-initiated cells regain normal growth behavior through contact with normal cells.
• Contact normalization is age-dependent and involves plasma membrane interactions.
• Tumor cell heterogeneity and age-related cancer incidence are explained by this principle.

Conclusions:

• The principle of order over heterogeneity offers a unifying framework for diverse biological processes.
• Cell-cell contact, not gap junctional communication, is crucial for ordered heterogeneity.
• Understanding ordered heterogeneity is key to deciphering normal development and tumor biology.