High expression of PRL-3 promotes cancer cell motility and liver metastasis in human colorectal cancer: a predictive molecular marker of metachronous liver and lung metastases.
OBJECTIVE
Overexpression of PRL-3 has been implicated in colorectal cancer metastases. We investigated the significance of PRL-3 expression in the progression and development of colorectal cancer.


METHODS
We transfected PRL-3-specific small interfering RNA into human colon cancer DLD-1 cells and analyzed its effect on proliferation, motility, and hepatic colonization. Using an in situ hybridization method, we examined the levels of PRL-3 expression in both primary (177 cases) and metastatic (92 cases) human colorectal cancers and elucidated the relationships with clinicopathological parameters including the incidence of metachronous liver and/or lung metastasis after curative surgery for primary tumor.


RESULTS
Transient down-regulation of PRL-3 expression in DLD-1 cells abrogated motility (in vitro) and hepatic colonization (in vivo), but no effect on the proliferation of these cells was observed. In human primary colorectal cancers, the frequency of up-regulated PRL-3 expression in cases with liver (84.4%) or lung (88.9%) metastasis was statistically higher than that in cases without either type of metastasis (liver, 35.9%; lung, 42.3%). In metastatic colorectal cancer lesions, high expression of PRL-3 was frequently detected (liver, 91.3%; lung, 100%). Interestingly, metachronous metastasis was observed more frequently in the cases with high PRL-3 expression (P < 0.0001).


CONCLUSIONS
These results indicate that PRL-3 expression in colorectal cancers may contribute to the establishment of liver metastasis, particularly at the step in which cancer cells leave the circulation to extravasate into the liver tissue. In addition, PRL-3 is expected to be a promising biomarker for identifying colorectal cancer patients at high risk for distant metastases.
Kato
Hirotaka
H
Division of Surgical Pathology, Department of Biomedical Informatics, Kobe University Graduate School of Medicine, Kobe, Japan.
Semba
Shuho
S
Miskad
Upik A
UA
Seo
Yasushi
Y
Kasuga
Masato
M
Yokozaki
Hiroshi
H
D000368:Aged; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005260:Female; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis* / Q000502:physiology*; D017403:In Situ Hybridization; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary*; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins; D011379:Prognosis; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis* / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D017874:Immediate-Early Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases