# Cell surface sphingomyelin: key role in cancer initiation, progression, and immune evasion.
> 細胞表面スフィンゴミエリンの過剰蓄積とがん発生・進行・免疫回避における役割


## Abstract

Excessive accumulation of sphingomyelin (SM) in the outer leaflet of the cell surface membrane is increasingly recognized as a central factor in cancer initiation, tumor growth, and evasion of host immunity. SM molecules form dense inter- and intramolecular hydrogen bond networks; when this network becomes overly rigid, it disrupts contact inhibition between cells, impairs intracellular and intercellular signaling, alters metabolic pathways, and reduces susceptibility to immune effectors. This review examines the mechanisms by which tumors escape immune surveillance, including deficient MHC class I expression, reduced Fas accessibility, and loss of natural killer cell checkpoint molecules. It further highlights the underappreciated role of SM synthesis and hydrolysis in carcinogenesis and metastasis promotion. Evidence is presented linking elevated surface SM levels to resistance to apoptosis, insensitivity to growth-suppressive signals, and immune escape, with discussion of potential novel strategies for cancer control.

### Mechanism

Excessive SM accumulation in the outer cell membrane leaflet creates an overly rigid hydrogen bond network, disrupting contact inhibition, impairing growth-suppressive signaling, and reducing immune cell recognition, thereby facilitating carcinogenesis and metastasis.

## Bibliographic

- **Authors**: Tallima H, Azzazy HME, El Ridi R
- **Journal**: Lipids Health Dis
- **Year**: 2021 (2021-10-31)
- **PMID**: [34717628](https://pubmed.ncbi.nlm.nih.gov/34717628/)
- **DOI**: [10.1186/s12944-021-01581-y](https://doi.org/10.1186/s12944-021-01581-y)
- **PMC**: [PMC8557557](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8557557/)
- **Study type**: review
- **Delivery route**: not specified
- **Effect reported**: not assessed

## Delivery context

The delivery route is not clearly identifiable from this paper. For hydrogen intake, inhalation is the most efficient route; inhalation, however, carries explosion risk (empirical LFL of 10%; high-concentration devices are not recommended).

## Safety notes

The delivery route is not clearly identifiable from this paper. For hydrogen intake, inhalation is the most efficient route; inhalation, however, carries explosion risk (empirical LFL of 10%; high-concentration devices are not recommended).

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)

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> **Cite as**: H2 Papers — PMID 34717628. https://h2-papers.org/en/papers/34717628
> **Source**: PubMed PMID [34717628](https://pubmed.ncbi.nlm.nih.gov/34717628/)