GROα promotes invasion of colorectal cancer cells.
Growth-regulated oncogene α (GROα) is a chemokine that plays a role not only in inflammation, but also in tumorigenesis. Accumulating data suggest that GROα is involved in tumor development and invasion in various malignancies, such as melanoma and bladder cancer. However, the pathophysiological role of GROα in human colorectal cancers (CRCs) is still unknown. We examined the expression of GROα and its pathophysiological significance in human CRCs and investigated whether GROα promotes the invasive potential of colon cancer cells. Specimens of 62 primary CRCs were examined immunohistochemically for GROα, and the relationship between GROα expression and clinicopathological features was investigated. The mRNA expression of GROα and its receptor CXCR2 was examined in ten colon cancer cell lines using RT-PCR. The effect of GROα protein on invasive potential was investigated in DLD-1 and LoVo cells using a Matrigel invasion chamber assay. Forty-nine (79%) of the 62 CRCs showed positive immunoreactivity for GROα. GROα expression was significantly associated with tumor size, tumor stage, depth of invasion, LN metastasis and patient survival (P=0.021, P<0.0001, P=0.0033, P<0.0001, P=0.039, respectively). Expression of CXCR2 mRNA was detectable in all ten colon cancer cell lines examined, whereas expression of GROα mRNA was detectable in six. Treatment with GROα protein significantly increased the number of invasive cells. In conclusion, GROα may play a pivotal role in the invasion of human CRCs.
Department of Surgical and Molecular Pathology, Dokkyo University School of Medicine, Shimotsuga, Tochigi, Japan.
Hideo
H
Ogata
Akira
A
Sekikawa
Hidetsugu
H
Yamagishi
Kazuhito
K
Ichikawa
Shigeki
S
Tomita
Johji
J
Imura
Yuichi
Y
Ito
Masanori
M
Fujita
Masahiro
M
Tsubaki
Hiroyuki
H
Kato
Takahiro
T
Fujimori
Hirokazu
H
Fukui
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000502:physiology; D018938:Caco-2 Cells; D049109:Cell Proliferation; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D019073:HT29 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; C475829:CXCL1 protein, human; D054360:Chemokine CXCL1