Discoidin domain receptor 1 is associated with poor prognosis of non-small cell lung carcinomas.
Discoidin domain receptors (DDRs) are a novel class of receptor tyrosine kinases that bind to several collagens and facilitate cell adhesion. DDR1 is involved in cancer invasion. However, very limited data are available on the aspect of clinical significance of DDR1 expression in cancer. The aim of this study was to investigate prognostic impact of DDR1 expression in non-small cell lung carcinoma (NSCLC). Tumor tissues from 171 NSCLC, including 86 squamous cell carcinomas, 69 adenocarcinomas, and 16 pure bronchioloalveolar carcinomas (BAC), were analyzed for expression of DDR1 using immunohistochemical staining. In addition, two lung adenocarcinoma cell lines (A549, H358) were transfected with two isoforms of DDR1, DDR1a and DDR1b, and then migration and invasion assays were carried out. DDR1 was expressed in 6 of 16 BAC (38%) and 95 of 155 invasive NSCLC (61%, p=0.065). DDR1 up-regulation tend to be more frequently observed in invasive adenocarcinoma (64%) compared to DDR1 expression in BAC (38%) (p=0.056). In invasive NSCLC, DDR1 expression was significantly correlated with lymph node metastasis (p=0.001). Overexpression of DDR1 in lung cancer cells resulted in a significant increase of cell motility and invasiveness (p<0.001) and the interaction of DDR1 with collagen facilitates the invasiveness of NSCLC cells. DDR1 overexpression produced an activation of MMP-9 in H358 cells. In conclusion, these findings indicate that up-regulation of DDR1 may contribute to the progression and poor prognosis of NSCLC and this effect may be associated with increased invasiveness.
Yang
Sun Ho
SH
Department of Pathology, Chonbuk National University Medical School, Jeonju 561-180, Korea.
Baek
Hyun Ah
HA
Lee
Ho Jin
HJ
Park
Ho Sung
HS
Jang
Kyu Yun
KY
Kang
Myoung Jae
MJ
Lee
Dong Geun
DG
Lee
Yong Chul
YC
Moon
Woo Sung
WS
Chung
Myoung Ja
MJ
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002448:Cell Adhesion / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D000070818:Discoidin Domain Receptors; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010997:Pleural Neoplasms / Q000378:metabolism / Q000556:secondary; D011379:Prognosis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011975:Receptors, Mitogen / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016019:Survival Analysis; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D011975:Receptors, Mitogen; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases