title: Osteopontin splice variants differentially exert clinicopathological features and biological functions in gastric cancer.
abstract: OBJECTIVE
  Gastric cancer (GC) remains a leading cause of death worldwide, and an elevated expression of osteopontin (OPN) may correlate with its poor survival. Alternative splicing of OPN can result in three isoforms, OPN-a, OPN-b and OPN-c. The aim of our current study is to examine the expression pattern and biological functions of OPN splice variants in GC.
  
  
  METHODS
  Firstly, we evaluated the expression of OPN splice variants in 7 gastric cell lines, 101 pairs of GC tissues and their adjacent non-tumor tissues by Quantative real-time PCR (QT-PCR). Gain-of-function experiments were subsequently performed to determine their diverse roles in malignant behaviors of GC. Besides, their differential effects on the regulation of crucial downstream molecules were further explored in the anti-apoptotic and pro-metastatic process.
  
  
  RESULTS
  We found that OPN-b is the dominant kind of OPN isoform in GC cell lines. Although the expression levels of three variants were all elevated in GC tissues, increased OPN-b or OPN-c expression could correlate with clinicopathological features. Functional analyses further showed that OPN-b most strongly promoted GC cell survival possibly by regulation of Bcl-2 family proteins and CD44v expressions. Moreover, OPN-c most effectively stimulated GC metastatic activity by increasing secretion of MMP-2, uPa, and IL-8.
  
  
  CONCLUSIONS
  Our results suggest that OPN splice variants differentially exert clinicopathological features and biological functions in GC. Therefore, focusing on specific OPN isoform could be a novel direction for developing diagnostic and therapeutic approaches in GC.
authors.affiliation: Shanghai Key Laboratory of Gastric Neoplasms, Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, 197 Rui Jin Er Road, Shanghai 200025, People's Republic of China.
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Tang
authors.forename: Jianfang
authors.initials: J
authors.lastname: Li
authors.forename: Beiqin
authors.initials: B
authors.lastname: Yu
authors.forename: Liping
authors.initials: L
authors.lastname: Su
authors.forename: Yingyan
authors.initials: Y
authors.lastname: Yu
authors.forename: Min
authors.initials: M
authors.lastname: Yan
authors.forename: Bingya
authors.initials: B
authors.lastname: Liu
authors.forename: Zhenggang
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D053495:Osteopontin / Q000235:genetics* / Q000378:metabolism*; D012326:RNA Splicing / Q000235:genetics / Q000502:physiology; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: D016209:Interleukin-8; D053495:Osteopontin; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2
keywords: OPN splice variants; apoptosis; biological function; clinicopathological feature; gastric cancer; metastasis.