# Basement membrane & tissue barriers

Source: https://onco.cc/pathways/basement-membrane-tissue-barriers/  
OnCo record `basement-membrane-tissue-barriers` (Pathway). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Every organ keeps its lining cells behind a thin, dense sheet of protein called the basement membrane. A tumour that has not crossed it is 'in situ' and essentially curable; crossing it is the moment cancer becomes invasive.

## Summary

Epithelia sit on a basement membrane of laminin, collagen IV, nidogen and perlecan anchored by integrins (α6β4 at hemidesmosomes) and dystroglycan, beneath which lies interstitial stroma. Polarity (apical-basal), E-cadherin junctions, and contact inhibition keep cells in place. Carcinoma in situ (DCIS, CIN3, Barrett's dysplasia) respects the sheet; invasion requires protease-driven breach (MMP2/9/14, uPA) at invadopodia, loss of polarity (PAR3, SCRIB), integrin switching and EMT-like changes, often assisted by CAFs and macrophages that widen the gap. Myoepithelial cells in breast add a second barrier. Staging encodes this (Tis versus T1) and screening programmes aim to find lesions before the breach.

## Fields

- Kind: Pathway
- Last checked: 2026-09-09
- Tags: mechanism; mechanics-atlas
- Analogy: A shop floor with a locked glass floor beneath it. Staff (epithelial cells) can be unruly upstairs and it is still contained; the emergency begins when someone cuts through the glass into the building services below, where the plumbing (blood and lymph vessels) runs.
- Interventions: Screening and excision of in situ disease (colposcopy, DCIS surgery, endoscopic resection) before the breach; HPV vaccination removes the commonest driver of cervical in situ lesions; MMP inhibitors failed clinically in the 1990s; invasion is now approached via FAK, integrin and stromal targets; Staging (Tis vs T1) and margins encode whether the barrier was crossed

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Basement_membrane
- Kelley et al., Traversing the basement membrane in vivo (J Cell Biol 2014): https://doi.org/10.1083/jcb.201311112

## Connected records

- cancers: [Bladder & urothelial cancer](https://onco.cc/cancers/urothelial/), [Cervical cancer](https://onco.cc/cancers/cervical/), [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Oesophageal cancer](https://onco.cc/cancers/esophageal/)
- technologies: [Colposcopy and excisional treatment (LEEP/LLETZ, cone)](https://onco.cc/technologies/colposcopy-excision/), [Endoscopic resection (EMR / ESD)](https://onco.cc/technologies/endoscopic-resection/), [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/), [HPV & HBV vaccination](https://onco.cc/technologies/hpv-vaccine/), [Thermal ablation and cryotherapy for cervical precancer](https://onco.cc/technologies/precancer-ablation/)
- pathways: [Epithelial-mesenchymal transition & drug efflux](https://onco.cc/pathways/emt/), [Field cancerisation](https://onco.cc/pathways/field-cancerisation/), [Invasion: proteases, adhesion & the invasive front](https://onco.cc/pathways/invasion-ecm-degradation/)
- terms: [Barrett's oesophagus](https://onco.cc/terms/barretts-esophagus/), [Cervical precancer (CIN, HSIL/LSIL)](https://onco.cc/terms/cin-hsil/), [Mechanical theory: stiffness, pressure and force as causes](https://onco.cc/terms/mechanical-theory-of-cancer/), [Stage shift](https://onco.cc/terms/stage-shift/), [Tissue organisation field theory (Sonnenschein and Soto)](https://onco.cc/terms/tissue-organisation-field-theory/), [TNM staging](https://onco.cc/terms/tnm-staging/)
- key papers: [Traversing the basement membrane in vivo: a diversity of strategies](https://onco.cc/key-papers/paper-kelley-j-cell-biol/)

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