Tumor-suppressor function of SPARC-like protein 1/Hevin in pancreatic cancer.
SPARC-like protein 1 (SPARCL1), a member of the SPARC family, is downregulated in various tumors. In the present study, the expression and localization of SPARCL1 were analyzed in a wide range of nontumorous and neoplastic pancreatic tissues by quantitative reverse transcription-polymerase chain reaction, laser capture microdissection, microarray analysis, and immunohistochemistry. For functional analysis, proliferation and invasion assays were used in cultured pancreatic cancer cells. Pancreatic ductal adenocarcinoma (PDAC) and other pancreatic neoplasms exhibited increased SPARCL1 mRNA levels compared to those of the normal pancreas. SPARCL1 mRNA levels were low to absent in microdissected and cultured pancreatic cancer cells, and promoter demethylation increased SPARCL1 levels only slightly in three of eight cell lines. SPARCL1 was observed in small capillaries in areas of inflammation/tumor growth and in some islet cells. In PDAC, 15.4% of vessels were SPARCL1-positive. In contrast, the percentage of SPARCL1-positive vessels was higher in chronic pancreatitis and benign and borderline pancreatic tumors. Recombinant SPARCL1 inhibited pancreatic cancer cell invasion and exerted moderate growth-inhibitory effects. In conclusion, SPARCL1 expression in pancreatic tissues is highly correlated with level of vascularity. Its anti-invasive effects and reduced expression in metastasis indicate tumor-suppressor function.
Esposito
Irene
I
Institute of Pathology, University of Heidelberg, Heidelberg, Germany.
Kayed
Hany
H
Keleg
Shereen
S
Giese
Thomas
T
Sage
E Helene
EH
Schirmacher
Peter
P
Friess
Helmut
H
Kleeff
Jörg
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D021441:Carcinoma, Pancreatic Ductal / Q000473:pathology / Q000517:prevention & control; D045744:Cell Line, Tumor; D016326:Extracellular Matrix Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000517:prevention & control*; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000502:physiology*
D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; C503126:SPARCL1 protein, human; D025521:Tumor Suppressor Proteins