Epithelial cell surface proteins (ECSP)

Epithelial cell surface proteins (ECSPs) constitute a broad and heterogeneous class of membrane-associated molecules located on the plasma membrane of epithelial cells (Royal Society Publishing, 2016; Endocrinology, 1999). This category encompasses a wide range of functional groups, including cell adhesion molecules (such as EpCAM and E-cadherin), growth factor receptors (such as EGFR and HER2), transporters, and enzymes (NIH, 2021; AME Groups, 2018; PNAS, 2012). These proteins are essential for maintaining the structural integrity of epithelial tissues, mediating cell-cell and cell-matrix interactions, and facilitating signal transduction in response to external stimuli (Endocrinology, 1999; J. Cell Biol., 2011). In clinical medicine, ECSPs are frequently utilized as diagnostic markers and therapeutic targets, particularly in oncology, where many are overexpressed in carcinomas (ResearchGate, 2020; NIH, 1999). For instance, EpCAM is a well-known target for the isolation of circulating tumor cells and for antibody-based therapies like catumaxomab (ResearchGate, 2020). Additionally, ECSPs often serve as receptors or attachment factors for various pathogens, including viruses like HIV-1 and bacteria like Helicobacter pylori, making them relevant in the study of infectious diseases (eScholarship, 2016; J. Cell Biol., 2011; Nature Comm, 2023). However, the therapeutic targeting of these proteins is often complicated by their expression in normal epithelial tissues, leading to potential on-target off-tumor toxicities (PNAS, 2012).

Other names

Epithelial surface markersEpithelial membrane proteinsEpithelial cell surface antigensEpithelial surface antigens

Drugs targeting specific epithelial cell surface proteins typically act through mechanisms such as inhibition of receptor-mediated signaling, induction of antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), or by serving as anchors for bispecific T-cell engagers to facilitate immune-mediated cell lysis (Endocrinology, 1999; PNAS, 2012).