Regulation of CD151 by hypoxia controls cell adhesion and metastasis in colorectal cancer.
OBJECTIVE
The first step of metastasis is the detachment of cancer cells from the surrounding matrix and neighboring cells; however, how cancer cells accomplish this process remains unclear. Thus, we aimed to investigate the underlying mechanism that controls the early event of metastasis.


METHODS
One hundred and thirty-seven paired colorectal carcinoma and normal colon tissues were examined by immunohistochemical staining and Western blot for the expression of CD151, a member of the tetraspanin family that plays important roles in cell adhesion and motility. The effect of CD151 on cancer cell adhesion was investigated under normoxia and hypoxia conditions.


RESULTS
The level of CD151 was down-regulated in colon cancer compared with the paired normal counterparts. Expression of CD151 was negatively regulated by hypoxia inducible factor-1-dependent hypoxic stress. Suppression of CD151 by hypoxia caused the detachment of cancer cells from the surrounding matrix and neighboring cells whereas restoration of CD151 expression during reoxygenation facilitated the adhesion capacity. Clinical examination further showed that metastasized cancer cells expressed a greater level of CD151 compared with that of primary tumor.


CONCLUSIONS
Regulation of CD151 by oxygen tension may play an important role in cancer metastasis by regulating the detachment from the primary site and homing in the secondary site.
Chien
Chun-Wei
CW
Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Lin
Shih-Chieh
SC
Lai
Yen-Yu
YY
Lin
Bo-Wen
BW
Lin
Shao-Chieh
SC
Lee
Jenq-Chang
JC
Tsai
Shaw-Jenq
SJ
D015703:Antigens, CD / Q000032:analysis* / Q000502:physiology; D002448:Cell Adhesion; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D009362:Neoplasm Metastasis; D060185:Tetraspanin 24
D015703:Antigens, CD; C554715:CD151 protein, human; D060185:Tetraspanin 24