Full-length cytokeratin 8 is released and circulates in patients with non-small cell lung cancer.
OBJECTIVE
Cytokeratin 8 (CK8) is a type II intermediate filament protein that is persistently expressed in most epithelial malignancies. Circulating CK-related polypeptides have commonly been used as tumor markers. While apoptosis is a mechanism of CK release, the molecular nature of circulating CKs is poorly understood. The aim is to clarify the dynamics of CK8 during apoptosis in vitro and the nature of circulating CK8 in patients with lung cancer.


METHODS
Extracellular release of CK8 was examined using A549 human non-small cell lung cancer (NSCLC) cells after apoptosis induction by etoposide. Serum samples from NSCLC patients were examined for circulating CK8 by ELISA (n = 60) and by immunoprecipitation (n = 9).


RESULTS
CK8 is released predominantly in full length from A549 cells undergoing apoptosis and is resistant to intracellular cleavage by caspases, unlike type I CK18, which is readily cleaved during apoptosis. Full-length CK8 is shown to constitute a considerable fraction of circulating CK8 in the serum of lung cancer patients.


CONCLUSIONS
Apoptosis causes extracellular release of full-length CK8 in NSCLC cells. CK8 circulates predominantly in full length in patients with NSCLC, illustrating the fundamental differences in protein processing between type I and type II CKs.
Ishii
Tomoya
T
First Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Bandoh
Shuji
S
Fujita
Jiro
J
Ohtsuki
Yuji
Y
Tojo
Yasunori
Y
Kanaji
Nobuhiro
N
Fukunaga
Yoko
Y
Ueda
Yutaka
Y
Ishida
Toshihiko
T
Kubo
Akihito
A
D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000097:blood* / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000378:metabolism; D045744:Cell Line, Tumor; D005047:Etoposide; D006801:Humans; D053533:Keratin-8 / Q000097:blood* / Q000378:metabolism; D008175:Lung Neoplasms / Q000097:blood* / Q000378:metabolism
D014408:Biomarkers, Tumor; D053533:Keratin-8; D005047:Etoposide