Binding of Recombinant Human Cytokeratin 19 to Laminin. A Possible Role in Interaction between Intermediate Filament Derived from Epithelial Cells and Extracellular Matrixes.

Abstract

ABSTRACT. Cytokeratin 8 (CK8) and cytokeratin 19 (CK19) is a specific cytoskeletal component of simple epithelia, including bronchial epithelial cells. We hypothesized that CK8 or CK19 released from epithelial cells may bind to and cause damage to extracellular matrixes through binding of anti-CK8 or anti-CK19 autoantibodies. In the present study, bindings of recombinant human CK8 and CK19 to laminin (both derived from mouse sarcoma cells and human), collagen, gelatin, and fibronectin were evaluated by a modified enzyme-linked immunosorbent assay (ELISA). In addition, binding of CK19 to laminin was also confirmed by inhibition assay. As a result, CK19 strongly bound to mouse laminin as well as human laminin. Pretreatment with laminin significantly reduced the binding of CK19 to laminin. However, binding of recombinant CK19 to laminin was not demonstrated by Western immunoblot, suggesting that SDS treatment of laminin diminished the binding. These results suggest that released CK19 from epithelial cells may have played a role in the damage of basement membrane by accumulation of an immune complex composed by CK19 and anti-CK19 autoantibody.

Suppression of Human Hepatoma Growth in vivo by a Monoclonal Antibody Against a Mr 45,000 Protein

“…Induction of keratin expression by laminin through its receptors on cell surface also was observed in HCC cells (24). Together with the finding that released keratin may cause basement membrane damage through binding to laminin (25), we hypothesize that the mAb T2-2 functions as an inhibitor of tumor cell migration and expansion through a laminin-mediated pathway that prevents matrix degradation and controls cell survival. Importantly, more details in cell signaling will need to be elucidatd.…”

Two pathologic types of hepatocellular carcinoma with lymph node metastasis with distinct prognosis on the basis of CK19 expression in tumor

“…7 Another study found that CK19 was correlated with vascular invasion in HCC. 24 We think this may be because of the differences in patient backgrounds; furthermore, those with CK19 may have had a low incidence of vascular invasion as its ICC-like presentation.…”

“…For example, Wu et al proposed that HCC could be classified by the presence or absence of CK19 expression, based on the evidence that HCC could originate from hepatic progenitor cells, 3,4,6 which could retain its biliary marker (cytokeratin 19 [CK19]) and progenitor cell marker (OV-6) during its differentiation into HCC. 6 CK19 was an important structural component of the epithelial cytoskeleton, generally expressed on cholangiocytes and intrahepatic cholangiocarcinoma (ICC) cells, 7,8 and HCCs positive for CK19 were found to have ICC-like differentiation associated with poorer differentiation, higher level of cellular proliferation, and poorer survival. 3,4,6,9 Although the incidence of lymph node metastasis (LNM) in operable HCC is as low as 1.7% to 7.5%, 10,11 lymph node (LN) status is a definite prognostic factor in HCC and leads to generally dismal survival rates.…”

Keratin 19 marks poor differentiation and a more aggressive behaviour in canine and human hepatocellular tumours

“…Interestingly, some authors suggest K19 provides tumour cells with a higher metastatic potential by promoting extracellular matrix degradation and/or cell mobility [31,32]. In a murine tumour model Chu et al established that cells expressing intact keratins had higher in vitro mobility and invasiveness [33].…”