Aberrant expression of collagen triple helix repeat containing 1 in human solid cancers.
OBJECTIVE
The collagen triple helix repeat containing 1 (CTHRC1) is a promigratory protein first found to be expressed during rat tissue repair process. Recent preliminary results revealed CTHRC(1) mRNA in melanoma and breast cancer. However, the full significance of CTHRC1 to human carcinogenesis remains unclear. This study is to further characterize the clinical and functional relevance of CTHRC1 in melanoma and other human solid cancers.


METHODS
First, semiquantitative immunohistochemistry analysis was done on 304 clinically annotated, paraffin-embedded biopsies representing different stages of melanoma progression. Then, short interfering RNA was used to inhibit expression of CTHRC1 protein for migration analysis on cultured melanoma cells. Finally, the CTHRC1 expression was surveyed in 310 samples representing 19 types of human solid cancers.


RESULTS
In benign nevi and noninvasive melanoma biopsies, there was little CTHRC1 protein expression. In contrast, in invasive primary melanomas, there was a significant increase of CTHRC1 protein (P < 0.01, chi(2) test). There was a further increase of CTHRC1 protein in metastatic melanoma specimens compared with nonmetastatic lesions (P < 0.01, chi(2) test). In addition, inhibition of CTHRC1 expression resulted in decreased cell migration in vitro. Finally, transcription survey in 19 types of human solid cancers revealed aberrant CTHRC1 expression in 16 cancer types, especially cancers of the gastrointestinal tract, lung, breast, thyroid, ovarian, cervix, liver, and the pancreas.


CONCLUSIONS
Aberrant expression of CTHRC1 is widely present in human solid cancers and seems to be associated with cancer tissue invasion and metastasis. It potentially plays important functional roles in cancer progression, perhaps by increasing cancer cell migration.
Tang
Liren
L
Department of Dermatology and Skin Science , University of British Columbia, Vancouver, British Columbia, Canada.
Dai
Derek L
DL
Su
Mingwan
M
Martinka
Magdalena
M
Li
Gang
G
Zhou
Youwen
Y
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D034622:RNA Interference; D011817:Rabbits; D020449:Repetitive Sequences, Amino Acid
C502426:CTHRC1 protein, human; D017931:DNA Primers; D016326:Extracellular Matrix Proteins