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NBME 22 Answers

nbme22/Block 3/Question#24

An 84-year-old woman comes to the physician because ...

Downregulation of E-cadherin

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submitted by d_holles(38),

This is a Pathoma Ch3 Q (p28).

Tumor invasion and spread

  1. Epithelial tumor cells are attached to one another by E-cadherin (cellular adhesion molecule). Downregulation of E-cadherin → dissociation of attached cells.
  2. Cells attach to laminin and destroy basement membrane via collagenase.
  3. Cells attach to fibronectin in the ECM and spread locally.
  4. Entrance into vascular or lymphatic spaces allows for metastasis.

https://imgur.com/a/FD16HiB





Pretty sure I’m missing something basic here. This was SCC invading basement membrane facilitated by what? The answer is downregulation of E-cadherin but I thought that’s for metastastses (FA 18 says so too.) I ticked decreased laminin receptors (incorrect) coz laminin was found in basement membrane. At least that was my reasoning. Any help appreciated. Thanks!

naughtyegg  Downregulating E-cadherin is the first step cancer takes toward metastasis because low E-cadherin helps invade the basement membrane -> eventually leads to spread of cancer elsewhere. Laminin is also involved but according to pathoma, cancer will actually attach to laminin in order to destroy the basement membrane. Idk if receptor up/downregulation happens, that might be a stretch. +1  
nuket0wn  per medbullets, there are increased laminin and integrin receptors. Also upregulated MMPs (matrix metallo-proteinases) to breakdown the basement membrane. +  
nwinkelmann  It makes sense that a tumor cell would increase their laminin, as opposed to decreasing, if attaching to laminin is what allows the cells to destroy the basement membrane. The more laminin, the more destruction possible. +  




Downregulating E-cadherin is the first step cancer takes toward metastasis because low E-cadherin helps invade the basement membrane -> eventually leads to spread of cancer elsewhere. Laminin is also involved but according to pathoma, cancer will actually attach to laminin in order to destroy the basement membrane. Idk if receptor up/downregulation happens, that might be a stretch.

nwinkelmann  It makes sense that a tumor cell would increase their laminin, as opposed to decreasing, if attaching to laminin is what allows the cells to destroy the basement membrane. The more laminin, the more destruction possible. +  




UWorld Question ID 1084 has a great explanation of this





According to Uworld.... 1.Tumor cells detach from the surrounding cells when adhesion molecule E-cadherin is low 2.Tumor cells adhere to basement membrane by increasing lamin 3.Tumor cells invade basement membrane by increasing proteolytic enzymes like metalloprotease