title: CXCL16 and CXCR6 in Ewing sarcoma family tumor.
abstract: Chemokines are a family of peptide mediators that play an essential role in cellular migration and intracellular communication in tumor cells as well as immune cells. We hypothesized that the CXCL16-CXCR6 ligand-receptor system plays an important role in Ewing sarcoma (ES) family tumor (ESFT) progression. Using real-time quantitative reverse transcription-polymerase chain reaction, we investigated the mRNA expression of CXCL16, CXCR6, and ADAM 10 in various cell lines. We also investigated the expression of CXCL16, CXCR6, ADAM 10, and ADAM 17 in tissue samples from 61 ESFT patients using immunohistochemistry. The mRNA expression levels of CXCL16 and CXCR6 in the ES cell line were higher than those in the other cell lines. Immunohistochemical staining revealed that CXCL16 and CXCR6 were highly expressed in tumor cells of ESFT and showed a positive correlation between them. The expression of CXCL16 and CXCR6 was associated with the occurrence of lung metastasis. Univariate analysis revealed that CXCL16 or CXCR6 expression was associated with worse prognosis of ESFT patients. In addition, CXCL16 and CXCR6 expression was associated with shorter overall survival irrespective of other prognostic factors. Our results suggest that the CXCL16/CXCR6 axis appears to be important in the progression of ESFT, resulting in more aggressive clinical behavior. Furthermore, there may be a decrease in the overall survival in ESFT patients who have tumors that stain strongly for CXCL16 and CXCR6.
authors: Department of Pathology, Graduate School of Medicine, Kyung Hee University, Seoul, South Korea.
authors: Ki Yong
authors: KY
authors: Na
authors: Department of Biomedical Science, College of Health Science, Korea University, Seoul, South Korea.
authors: Hyun-Sook
authors: HS
authors: Kim
authors: Department of Biomedical Laboratory Science, College of Health Science, Cheongju University, Chungbuk, South Korea.
authors: Woon-Won
authors: WW
authors: Jung
authors: Department of Pathology, Kyung Hee University Hospital, Kyung Hee University, Seoul, South Korea.
authors: Ji-Youn
authors: JY
authors: Sung
authors: Laboratory of Orthopedic Pathology, Paraguay 2302, 11 Floor, of: 1. C1121ABL, Buenos Aires, Argentina.
authors: Ricardo Karam
authors: RK
authors: Kalil
authors: Department of Pathology, Graduate School of Medicine, Kyung Hee University, Seoul, South Korea.
authors: Youn Wha
authors: YW
authors: Kim
authors: Department of Pathology, Graduate School of Medicine, Kyung Hee University, Seoul, South Korea. Electronic address: ykpark@khmc.or.kr.
authors: Yong-Koo
authors: YK
authors: Park
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D001859:Bone Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000032:analysis / Q000096:biosynthesis*; D002648:Child; D002675:Child, Preschool; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine / Q000032:analysis / Q000096:biosynthesis*; D051116:Receptors, Scavenger / Q000032:analysis / Q000096:biosynthesis*; D011991:Receptors, Virus / Q000032:analysis / Q000096:biosynthesis*; D012512:Sarcoma, Ewing / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D059467:Transcriptome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C423727:CXCL16 protein, human; C106330:CXCR6 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D012333:RNA, Messenger; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D051116:Receptors, Scavenger; D011991:Receptors, Virus
keywords: CXCL16; CXCR6; Ewing sarcoma; Ewing sarcoma family tumor