Morphostats: a missing concept in cancer biology.

Area of Science:

• Developmental Biology
• Tissue Engineering
• Cancer Biology

Background:

• Epithelial tissues maintain complex microarchitecture despite cell turnover.
• Metaplasia and transdifferentiation suggest loss of microarchitectural control.
• Morphogens guide development, but adult tissue maintenance requires similar regulators.

Discussion:

• Postulates morphogen-like molecules, termed 'morphostats,' in adult epithelia.
• Morphostats, potentially from adjacent mesenchymal cells, maintain tissue structure.
• Evidence includes rarity of metaplasia, carcinogenesis at epithelial junctions, and fibroblast roles.

Key Insights:

• Morphostats may function via diffusion gradients, influencing cell adhesion, apoptosis, and proliferation.
• Proposes a two-hit cancer model: epithelial mutation (dysplasia) and mesenchymal mutation (microarchitectural disruption).
• Mesenchymal mutations can cause microarchitectural issues without epithelial dysplasia, and vice versa.

Outlook:

• Disruption of morphostat function is implicated as a key event in carcinogenesis.
• Further research into morphostat function could reveal new therapeutic targets for cancer.
• Understanding morphostat-mesenchymal interactions is crucial for tissue regeneration and cancer prevention.