Soluble E-cadherin: more than a symptom of disease

Abstract

Epithelial (E)-cadherin is a homophilic adhesion molecule which is responsible for maintenance of baso-lateral cell adhesion and polarity. E-cadherin can be lost from the cell surface by proteolytic cleavage, resulting in the generation of an 80kDa fragment referred to a soluble E-cadherin (sE-cad). Although originally discovered in the conditioned media of breast cancer cells and later verified in the fluids of cancer patients, today sE-cad has been reported in patients with viral and bacterial infections, organ failure, and benign disease. The proteases implicated in this cleavage event include members of the disintegrin family (ADAM10 and 15), bacterial proteases (gingipains and BFT), cathepsins (B, L, S), matrix metalloproteases (MMP-2, 3, 7, 9, and 14), Kallikrein-7 (KLK7), and plasmin. Stimulus that induces sE-cad generation by ADAMs, MMPs, KLK7, and plasmin in vitro ranges from serum withdrawal to pro-inflammatory cytokines to growth factors. The cellular or physiologic consequences of sE-cad accumulation include the disruption of adherens junctions, cellular migration and invasion, induction of MMPs, as well as cell signaling, suggesting that sE-cad may contribute to disease progression.

Cooperative cell invasion: matrix metalloproteinase–mediated incorporation between cells

“…Given the cell–cell adhesion exhibited by the IMR32 MCS, we considered whether the IMR32 cell–cell interactions presented a barrier to SHEP invasion. On the basis of previous reports that MMPs can cleave cell–cell adhesions (Grabowska and Day, 2012), we asked whether MMP activity might be required for SHEPs to break through the barrier presented by IMR32 cell–cell adhesion. To test this, we adapted a previous method for analyzing the incorporation of one cell type into layers of a second cell type (Hamilla et al.…”

Senescence marker killer cell lectin-like receptor G1 (KLRG1) contributes to TNF-α production by interaction with its soluble E-cadherin ligand in chronically inflamed joints

“…The ligand for KLRG1, E-cadherin, can be shed from the cell surface by proteolytic cleavage resulting in its soluble 80 kDa fragment sE-cadherin 33. Hence, sE-cadherin levels were compared in paired plasma and cell-free SF samples from the SpA/RA (n=21) and crystal-induced arthritis patients (n=8).…”

Altered gene expression patterns during the initiation and promotion stages of neonatally diethylstilbestrol-induced hyperplasia/dysplasia/neoplasia in the hamster uterus

“…However, evidence does exist for a promoting role of E-cadherin in some aspects of carcinogenesis [28, 59]. Furthermore, extracellular “shedding” of E-cadherin proteolytic fragments does occur and evidence indicates that the soluble fragments can influence various cell dynamics including junctional integrity, migration, invasion, and signal initiation [60]. Whether altered levels of such fragments, for instance the 103 and 23 kDa forms we detected in our WB analyses, are involved in the uterine dysplasia/neoplasia phenomenon deserves further attention.…”