Tumor interstitium and tumor cell membranes

The tumor interstitium and tumor cell membranes constitute the physical and chemical landscape of the tumor microenvironment (TME). The interstitium is composed of the extracellular matrix (ECM) and interstitial fluid, which in solid tumors often exhibits high hydrostatic pressure and an acidic pH. This environment creates a significant physiological barrier to the delivery of therapeutic agents, particularly large molecules like monoclonal antibodies (Jain, 1987, Cancer Research). Tumor cell membranes act as the critical interface for cellular signaling and are the primary site for the localization of many oncogenic receptors and transporters (Sliwkowski & Mellman, 2013, Science). Drugs must successfully traverse the interstitial space and interact with or cross the cell membrane to exert their effects. Therapeutic strategies, such as the use of hyaluronidase to reduce interstitial pressure, aim to modulate these compartments to enhance the penetration and efficacy of co-administered chemotherapies (Provenzano et al., 2012, Cancer Cell). Additionally, the unique lipid composition and surface charge of tumor cell membranes are exploited for the development of membrane-disrupting peptides and targeted liposomes (Helmlinger et al., 1997, Nature Medicine). Understanding the interplay between these compartments is essential for optimizing drug pharmacokinetics and overcoming resistance in solid tumors.

Other names

Tumor microenvironmentTMEExtracellular matrixNeoplastic cell surfaceInterstitial space

Enzymatic degradation of extracellular matrix components, reduction of interstitial fluid pressure, and receptor-mediated binding to the cell surface.