During metastasis, tumor cells must intravasate, survive in circulation, and extravasate at distant sites. The step that is rate-limiting and requires tumor cells to remodel the basement membrane involves secretion of which enzyme class?

• A Serine proteases (urokinase-type plasminogen activator)
• B Cysteine cathepsins acting exclusively in acidic lysosomes
• C Hyaluronidase dissolving the glycocalyx of endothelial cells
• D Matrix metalloproteinases (particularly MMP-2 and MMP-9) ✓

Explanation

Basement membrane degradation — critical for both local invasion (intravasation) and extravasation at metastatic sites — depends primarily on matrix metalloproteinases, especially the gelatinases MMP-2 (gelatinase A, degrades type IV collagen) and MMP-9 (gelatinase B). Type IV collagen is the principal structural component of basement membranes. MMPs are secreted by tumor cells and also induced in stromal fibroblasts and macrophages by tumor-derived signals. Urokinase (uPA) activates plasminogen to plasmin, which also degrades ECM but works upstream by activating MMPs. Cathepsins operate in acidic compartments; hyaluronidase targets interstitial matrix.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.