Orthotopic implantation mouse model and cDNA microarray analysis indicates several genes potentially involved in lymph node metastasis of colorectal cancer.
In colorectal cancer (CRC) patients, metastasis to the regional lymph node (LN) is an important first step in the dissemination of cancers. To identify the genes possibly involved in LN metastasis of CRC, we analyzed LN metastases in an orthotopic implantation mouse model with 22 CRC cell lines using Matrigel, an extracellular matrix protein derived from mice sarcoma, and combined the data with gene expression profiles of cDNA microarray of those cell lines. With this implantation analysis, the incidence of LN metastasis was 60% in 228 orthotopically implanted mice and varied from 100% to 0% among the cell lines. KM12c and Clone A showed LN metastasis in all orthotopically implanted mice, but DLD-1, HCT-8, and SW948 did not show LN metastases at all. In contrast, the incidence of liver and lung metastasis in 22 CRC cell lines was 13% and 1%, respectively. Combining those data with cDNA microarray in vitro, we isolated 636 genes that were differentially expressed depending on the incidence of LN metastasis. Among those genes, the expression level of ring finger protein 125 (RNF125), previously known as an E3 ubiquitin ligase in T cell activation, was significantly different between primary tumors in Stage III CRC patients with LN metastasis and Stage II patients without LN metastasis. In conclusion, the orthotopic implantation mice model with Matrigel was useful, and we isolated candidate genes such as RNF125 that possibly play an important role in LN metastasis of CRC cells.
Sasaki
Hiroyuki
H
Division of Biological-Regulation and Oncology, Tohoku University Graduate School of Medicine, Miyagi 980-8574, Japan.
Miura
Koh
K
Horii
Akira
A
Kaneko
Naoyuki
N
Fujibuchi
Wataru
W
Kiseleva
Larisa
L
Gu
Zhaodi
Z
Murata
Yukio
Y
Karasawa
Hideaki
H
Mizoi
Takayuki
T
Kobayashi
Terutada
T
Kinouchi
Makoto
M
Ohnuma
Shinobu
S
Yazaki
Nobuki
N
Unno
Michiaki
M
Sasaki
Iwao
I
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015179:Colorectal Neoplasms / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D008207:Lymphatic Metastasis / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis