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  • Review Article
  • Published:

Morphogens, morphostats, microarchitecture and malignancy

Nature Reviews Cancer volume 7, pages 464–474 (2007)Cite this article

Key Points

  • Morphogenetic fields organize tissue morphology and development in the embryo.

  • Adult tissues need to solve the same problems as embryonic tissue: maintaining form even as constituent cells proliferate, move, differentiate and die.

  • The maintenance of epithelial tissues requires, like morphogenesis, a method of relating cell position to function. A morphogenetic field is an evolutionarily well-tried mechanism.

  • By analogy with morphogens, morphostats maintain normal tissue microarchitecture in the adult.

  • In addition to established molecular abnormalities, the most prominent feature of cancer is the disruption of tissue microarchitecture.

  • Cancer arises more readily in tissues where morphostatic fields fail, in tissues removed from their normal morphostatic fields, and in areas situated at the junction of two tissues where morphostatic fields compete or conflict.

  • Known morphogens are agents that are capable of creating morphostatic fields; disruption of morphogen signalling is increasingly implicated in the aetiology of various cancers.

  • Morphostats most plausibly originate in stem cells and in stromal cells that are adjacent to epithelia.

  • Various testable hypotheses follow on from this, most notably, that some cancers will arise as the result of a different two-hit model (either mutation or hypermethylation of genes) — one in a stromal cell and one in the epithelium.

Abstract

Morphogenetic fields organize tissue morphology in the embryo. By analogy, morphostatic fields maintain normal cell behaviour and normal tissue microarchitecture in the adult. The most prominent feature of cancer is the disruption of tissue microarchitecture. Cancer occurs much more frequently when morphostatic influences fail (metaplasia) or at the junction of two different morphostatic fields. This Review will describe what we know about morphostats and morphostasis, discuss the evidence for the role of disruption of morphostasis in malignancy, and address some testable hypotheses.

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Figure 1: Morphogens and the regulation of development and differentiation.

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Glossary

Angiogenesis

The formation of new blood vessels.

Major histocompatibility complex

(MHC). A genetic region encoding proteins that are involved in antigen presentation to T cells. MHC class I molecules that are bound to a peptide are recognized by the T-cell receptors of CD8+ T cells.

Condensation

A cellular aggregation with a higher number of cells per unit volume than the surrounding tissue that is characteristic of the early stages of limb and organ morphogenesis.

Stromal

Of the stroma, which is an organ compartment that serves as the connective tissue framework; it includes fibroblasts, immune defence cells and fat cells.

Metaplasia

Metaplasia involves the proliferation of a cell type that is not commonly found in a particular tissue space. For example, squamous metaplasia occurs in the airways of smokers and represents the replacement of columnar epithelial cells with squamous cells.

Epithelial–mesenchymal transition

Conversion from an epithelial to a mesenchymal phenotype, which is a normal component of embryonic development. In carcinomas, this transformation results in altered cell morphology, the expression of mesenchymal proteins, and increased invasiveness.

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Potter, J. Morphogens, morphostats, microarchitecture and malignancy. Nat Rev Cancer 7, 464–474 (2007). https://doi.org/10.1038/nrc2146

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