Differential expression and function of caveolin-1 in human gastric cancer progression.
Caveolin-1 is a scaffold protein of caveolae that acts as a tumor modulator by interacting with cell adhesion molecules and signaling receptors. The role of caveolin-1 in the pathogenesis of gastric cancer (GC) is currently unknown. We show by confocal immunofluorescence microscopy and immunohistochemistry of biopsies from GC patients (n = 41) that the nonneoplastic mucosa expressed caveolin-1 in foveolar epithelial cells and adjacent connective tissue. GC cells of only 3 of 41 (7%) patients expressed caveolin-1 and were all of the intestinal type. Quantitative PCR and Western blotting confirmed that, compared with nonneoplastic tissue, the overall caveolin-1 mRNA was decreased in 14 of 19 (74%) GC patients and protein in 7 of 13 (54%), respectively. Strong caveolin-1 reactivity was found in the nonepithelial compartment (myocytes, fibroblasts, perineural, and endothelial cells) in both tumor-free and GC samples. In a series of human GC cell lines, caveolin-1 expression was low in cells derived from a primary tumor (AGS and SNU-1) but was increased in cell lines originating from distant metastases (MKN-7, MKN-45, NCI-N87, KATO-III, and SNU-5). Ectopic expression of caveolin-1 in AGS cells decreased proliferation but promoted anchorage-independent growth and survival. RNAi-mediated knockdown of endogenous caveolin-1 in MKN-45 cells accelerated cell growth. These data indicate that caveolin-1 exhibits a stage-dependent differential expression and function in GC and may thereby contribute to its pathogenesis.
Burgermeister
Elke
E
Department of Medicine II, Klinikum rechts der Isar, Technical University of München, Munich, Germany.
Xing
Xiangbin
X
Röcken
Christoph
C
Juhasz
Mark
M
Chen
Jie
J
Hiber
Michaela
M
Mair
Katrin
K
Shatz
Maria
M
Liscovitch
Moti
M
Schmid
Roland M
RM
Ebert
Matthias P A
MP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051242:Caveolin 1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D021962:Membrane Microdomains / Q000378:metabolism; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D051242:Caveolin 1; D012333:RNA, Messenger