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Basement membrane & tissue barriers

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.

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.

In one picture

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.

Diagram

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Polarised epitheliumE-cadherin junctionsBasement membraneIntegrins / hemidesmosomesCarcinoma in situMMPs, uPA, invadopodiaStroma, vesselsInvasive carcinomaMyoepithelial layeractivatesinhibitsdruggable target (click)hit by selected productescape route

How drugs attack it

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  • 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

Connected

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Pages like this

not linked directly; found by shared links

cancers

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Bladder & urothelial cancerCervical cancerHR-positive / HER2-negative breast cancerOesophageal cancer

technologies

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Colposcopy and excisional treatment (LEEP/LLETZ, cone)Endoscopic resection (EMR / ESD)Histopathology & immunohistochemistryHPV & HBV vaccinationThermal ablation and cryotherapy for cervical precancer

pathways

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Epithelial–mesenchymal transition & drug effluxField cancerisationInvasion: proteases, adhesion & the invasive front

terms

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Barrett's oesophagusCervical precancer (CIN, HSIL/LSIL)Stage shiftTNM staging