Increased claudin-1 protein expression in hepatic metastatic lesions of colorectal cancer.
BACKGROUND
The molecular and morphological alterations of the tight junctions in hepatic metastatic lesions are poorly understood. The possible involvement of claudin-1 (CL-1), which is one of the major tight junctional proteins, was investigated in the tumorigenesis of hepatic metastasis in patients with colorectal cancer (CRC).


METHODS
A total of 14 patients with hepatic metastasis of CRC who underwent surgical treatment from January 2007 until December 2010 at the Kurume University Hospital in Fukuoka, were examined. CRC tissue specimens were analyzed to determine whether the levels of CL-1 correlated with clinicopathological factors and to determine the roles of CL-1, β-catenin, and E-cadherin in the alterations of the tight junctions during tumorigenesis.


RESULTS
In seven cases, the tumors were located in the colon, while the other seven tumors were found in the rectum. There were eight cases of synchronous liver metastasis, while there were six cases of metachronous liver metastasis. The levels of the CL-1 protein were up-regulated in CRC and in hepatic metastatic lesions. The levels of β-catenin were positive or up-regulated in the primary CRC lesions and in hepatic metastatic lesions. Despite the finding that the levels of E-cadherin were decreased in CRC, they were clearly up-regulated in hepatic metastatic lesions in this study.


CONCLUSIONS
This study demonstrated that CL-1 levels were up-regulated in liver metastatic lesions from primary CRC lesions. Moreover, the levels of E-cadherin were increased in liver metastatic lesions, which may point to the existence of interactions between CL-1 and E-cadherin in hepatic metastatic lesions. These observations suggest that CL-1 plays a pivotal role in the regulation of cellular morphology and in the behavior of metastatic processes in CRC.
Department of Surgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, Japan. kinugasa_tetsushi@med.kurume-u.ac.jp
Tetsushi
T
Kinugasa
Yoshito
Y
Akagi
Takafumi
T
Ochi
Natsuki
N
Tanaka
Akihiko
A
Kawahara
Yoshinobu
Y
Ishibashi
Yukito
Y
Gotanda
Keizo
K
Yamaguchi
Ichitarou
I
Shiratuchi
Yousuke
Y
Oka
Masayoshi
M
Kage
Kazuo
K
Shirouzu
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D015820:Cadherins / Q000096:biosynthesis; D062445:Claudin-1; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism* / Q000556:secondary; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D015854:Up-Regulation; D051176:beta Catenin / Q000096:biosynthesis
D014408:Biomarkers, Tumor; C568108:CLDN1 protein, human; D015820:Cadherins; D062445:Claudin-1; D008565:Membrane Proteins; D051176:beta Catenin