Abnormal expression and processing of the proprotein convertases PC1 and PC2 in human colorectal liver metastases.
BACKGROUND
The family of proprotein convertases has been recently implicated in tumorigenesis and metastasis in animal models. However, these studies have not yet been completely corroborated in human tumors.


METHODS
Using RT PCR, immunoblot and immunohistochemistry we assessed the presence and the processing patterns of the convertases PC1 and PC2 as well as the PC2 specific chaperone 7B2 in human liver metastases originating from colorectal cancer and compared them to unaffected and normal liver. Furthermore, we assessed the presence and processing profiles of PC1, PC2 and 7B2 in primary colon cancers.


RESULTS
mRNA, protein expression, and protein cleavage profiles of proprotein convertases 1 and 2 are altered in liver colorectal metastasis, compared to unaffected and normal liver. Active PC1 protein is overexpressed in tumor, correlating with its mRNA profile. Moreover, the enhanced PC2 processing pattern in tumor correlates with the overexpression of its specific binding protein 7B2. These results were corroborated by immunohistochemistry. The specific and uniform convertase pattern observed in the metastases was present only in a fraction of primary colon cancers.


CONCLUSIONS
The uniformly altered proprotein convertase profile in liver metastases is observed only in a fraction of primary colon cancers, suggesting possible selection processes involving PCs during metastasis as well as an active role of PCs in liver metastasis. In addition, the exclusive presence of 7B2 in metastatic tumors may represent a new target for early diagnosis, prognosis and/or treatment.
Tzimas
George N
GN
Transplant and Hepato-Pancreatobiliary Research Group, McGill University Health Center, McGill University, S.10.26, Montreal, H3A1A1, Canada. george_tzimas@hotmail.com
Chevet
Eric
E
Jenna
Sarah
S
Nguyên
Duc Thang
DT
Khatib
Abdel M
AM
Marcus
Victoria
V
Zhang
Yi
Y
Chrétien
Michel
M
Seidah
Nabil
N
Metrakos
Peter
P
D003110:Colonic Neoplasms / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D017931:DNA Primers / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism* / Q000556:secondary*; D008954:Models, Biological; D009362:Neoplasm Metastasis; D016133:Polymerase Chain Reaction; D011379:Prognosis; D045664:Proprotein Convertase 1 / Q000096:biosynthesis*; D045706:Proprotein Convertase 2 / Q000096:biosynthesis*; D011485:Protein Binding; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D012333:RNA, Messenger; D012313:RNA; D045664:Proprotein Convertase 1; D045706:Proprotein Convertase 2